Malignant Mesothelioma and Erionite
Cancer has been known for millennia, but the understanding we have of its
origins and causes are comparatively recent. Ancient Egyptians first recorded
cancer as a disease some 4500 years ago. However, it wasn’t until the 18th
century that observations on environmental cancers were made, as people started
to look for a connection between certain environments, including working
practices and human cancer incidence patterns. The idea emerged that the causes
of cancer may be divided roughly into two broad categories: exogenous, which is
envi¬ronmental and occupational, and endogenous, which is something inherent in
the person. While this has been a useful distinction, advances in genetics now
seem to be blurring the boundary. The result is that cancer research has
concentrated on the identification of envi¬ronmental and occupational causes of
human cancer. By the late 19th century the study of cancer tissues had revealed
that cancer cells were markedly different in biology and cell structures when
compared with the normal cells in the surrounding tissue. During the 20th
century, the research in cancer increased in an almost exponential fashion.
Advances in genetics, biochemistry, and molecular biology have begun to allow
some insight into what was happening when a normal cell was changed into a
cancerous one and often why it happened. Gene therapy approaches for inherited
and acquired lung diseases are reviewed else¬where (1). Modification of erionite
and its effects on in vitro activity is discussed in Brown et al (2). The
genetic susceptibility to mesothelioma has been introduced and discussed in the
literature (3–6).
Cancer can take many forms and is usually named after the cell type from which
it is transformed. Once a cancer cell has arisen, clonal expansion without
regard for the surrounding tissue, accounts for the clinical symptoms of the
disease. As the tumor grows, continuous dedifferentiation occurs and cells break
away to form new cancers at other sites in the body. It is this metastatic
growth that accounts for most of the mortality from this disease. A few tumor
types are so aggressive in their development that they kill the host before
metas¬tasis even begins. One such cancer is mesothelioma, which is a cancer of
the lining of the body cavity and named for its development from
the mesothelium. Although these cancers had been known for a long time, only in
the past 40 to 50 years have they been accepted as real mesothelial neoplasms,
and not secondary tumors. In 1960, Wagner et al (7) described 33 cases of
malignant pleural mesothelioma that they believed had developed through
environmental exposure to crocido-lite, which is blue asbestos. Up to this time,
human tumors for which an external cause had been suggested were believed to
arise through heavy occupational exposure. That tumors could arise through
specific environmental exposure meant that a very much larger population could
be at risk.
Then, about 30 years ago, the fear that this discovery engendered was underlined
when Professor Izzetin Baris identified large numbers of human mesotheliomas in
several villages in central Turkey, in the region known as Central Anatolia.
This time, crocidolite, or indeed any other amphibole mineral, was not to blame.
Such minerals were not found in this part of the country, although it did seem
probable that a fibrous mineral was responsible for the unprecedented level of
disease. Examination of the volcanic rock formations that dominate this part of
the country revealed the presence of a fibrous zeolite known as erion-ite, which
contained a high percentage of respirable fibers. Animal experiments have now
shown that this may be the most potent natural mineral carcinogen in nature. It
was far more carcinogenic than crocid-olite. With this knowledge, Baris and his
colleagues have demonstrated that a major cause of the mesotheliomas (in some
cases five out of six family members have presented with mesothelioma) is the
erionite. Any role it may have in other cancers is unclear, but in some
Cap-padocian villages in Central Anatolia cancer is the predominant cause of
death, maybe as high as 80% of total deaths, and some 50% of these deaths result
from mesothelioma. Since the villagers have constructed their houses from tuffs
carved from the often erionite-rich volcanic rock, and because they till the
ground containing respirable fibers of erionite, they are exposed to the fibers
continuously, indoors and out, throughout their lives. Current attempts at
cancer prevention in these villages (now a unique human laboratory) has led to
research efforts involving molecular and cellular changes in mineral fiber
carcinogen-esis, carcinogen avoidance techniques, human lifestyle analysis,
nutri¬tional consumption patterns, and chemical/drug prevention concepts. The
Turkish Ministry of Health has begun to support efforts aimed at reducing this
preventable human cancer problem by establishing hos¬pitals in central Turkey
and by sponsoring international meetings in attempts to understand better
environment and cancer interrelation¬ships and to identify possible means of
prevention.
The problems of natural environmental pollution by mineral fibers are not unique
to Turkey, although Turkey has suffered more than any other country. Also,
considering the concept of nutritional prevention of cancers, understanding and
ensuring good nutrition is a global concern. However, Turkey is a geographically
vast country with a large heterogeneous rural community. Most Turkish people
survive through subsistence farming, and have a variety of foods, which is a
luxury few can experience.
Brief History of the Region
The Cappadocia, “Katpatuka” in Old Persian, means land of beautiful horses.
Archaeologic records indicate that Hittites, Phrygians, Persians, and Romans
populated the region. After Christianity was accepted as a religion, a monastic
life in the region started about 350 A.D. Sub¬sequently, Cappadocia was occupied
by Arabs during the 7th and 8th centuries, and Byzantium succeeded the Arabs
toward the mid-9th century. In 1071, the Anatolian Seljuks diminished the
Eastern Byzantium Empire in the Central and Eastern Anatolia provinces. From the
14th century onward, the Ottomans replaced the Seljuks in ruling the region. All
empires left their cultural influences as a precious heritage: more than 400
rock-hewn churches, the remains of Early Christian and Byzantine art, and the
Ottomans’ hans, caravan serais, medreses, turbes, and mosques.
It is believed that zeolitic tuff was first used during the Roman empire to
build houses, construct roads, sewage channels, and milestones (8,9). Therefore,
it is logical to assume that exposure to eri-onite has been continuous and
widespread. Thus the diseases asso¬ciated with erionite have occurred over many
centuries in these regions.
Zeolite-Group Minerals
In general, zeolite-group minerals have excellent physical and chemi¬cal
properties and they are used widely in industry. However, a fibrous form of
zeolite, called erionite, has been proven to be the most toxic mineral in
humans.
The word zeolite comes from the Greek word meaning boiling stone, because of the
loss of water when it is heated. Cronsted discovered stilbite, a zeolite-type
mineral, in 1756. Currently, a zeolite mineral is defined as a crystalline
substance with a structure characterized by a framework of several linked
tetrahedra, each consisting of four O atoms surrounding a cation. In the
hydrated phases, dehydration occurs at temperatures mostly below about 400°C and
is largely reversible. The framework may be interrupted by (OH, F) groups; these
occupy a tetrahedron apex that is not shared with adjacent tetrahedra. The
tetrahedral arrangement forms lattice structures with relatively large cavities
connected by channels. These cavities contain H2O mole¬cules, and monovalent and
divalent cations that balance the charge resulting from a trivalent aluminum ion
replacing a quadrivalent silicon ion in the tetrahedra. The cations in the
cavities can be exchanged with other cations including mainly sodium, potassium,
calcium, magne¬sium, and also less often barium, strontium, copper, zinc, lead,
silver, rubidium, cesium, and ammonium.
The zeolite group of minerals included 32 naturally occurring min¬erals before
1997. The number of minerals almost tripled when the zeolite-group minerals were
reclassified and 13 of them rose to a series status (10,11).
Mineralogy of Erionite
Eakle defined erionite from Durkee, Oregon, in 1898. The mineral occurred as
white woolly fibers associated with opal in cavities in rhy-olitic welded ash
flow tuff. Eakle proposed the name erionite, from the Greek word for wool,
because of its woolly aspect.
Earlier erionite studies included Deffeyes (12), Staples and Gard (13), Ames
(14), Eberly (15), and Kawahara and Curien (16). Deffeyes (12) improved the
crystallographic data of erionite and described erionite from the northern
Jersey Valley, Sonoma Range Quadrangle, Nevada; Shoshone Range and valley of
Reese River, Nevada; Pine Valley, Nevada; east of Sand Draw, Wyoming; and White
River formation, South Dakota.
Erionite, in different parts of the world, has been studied: in the United
States by Deffeyes (12), in Italy by Passaglia et al (17) and Passaglia and
Tagliavini (18), in Germany by Rinaldi (19), in Crimea by Suprychev and
Prokhorov (20), in Antarctica by Vezzalini et al (21), in Mexico by Garcia-Sosa
and Rios-Solache (22), and in Japan by Kawahara et al (23), Harada et al (24),
Shimazu and Yoshida (25), and Shimazu and Mizoda (26).
The morphology of erionite is hexagonal prisms terminated with the basal
pinacoid. Erionite usually occurs as thin fibers, often forming a compact felt,
sometimes with a delicate woolly appearance. The occur¬rence of intergrowth with
offretite is common, because both minerals have similar structures. Sometimes a
single erionite crystal contains some stacking faults of the offretite, as shown
by the transmission elec¬tron microscopy (TEM) technique (27). Macro
intergrowths have been described by Rinaldi (19). Fibrous erionite-offretite
intergrowths over levyne lamellae have been observed by Gottardi and Galli (28).
Definition of Erionite Series
Three types of erionite are described as erionite-Na, the type specimen by
Sheppard and Gude (29), erionite-K, the type specimen by Passaglia et al (30),
and erionite-Ca, the type specimen by Harada et al (24). If all reliable
chemical analyses of erionite and offretites available in the lit¬erature are
plotted in a discriminatory diagram based on the above chemical parameters, it
is evident that none of the proposed criteria satisfactorily defines appropriate
compositional fields apt to describe the literature information (30). Chemical
analyses are considered to be reliable
if (Si
+ Al)
= 36, on the basis of 72 atoms, and balance
error (E)
< 10%. E% (31) is
100
¥
[(A1
+
Fe)ob
-Alth]/Alth
where Alth
= Na
+ K
+ 2
¥
(Ca
+
Mg
+
Sr
+
Ba).
Studies of the crystal structure and crystal chemistry of erionite in general,
but not Turkish erionite, include those of Alberti et al (32), Gualteri et al
(33), and Passaglia and Sheppard (34).
Geologic and Medical Studies of the Region
Previous geologic studies of the area include Sassano (35), Beekman (36),
Pasquare (37), Batum (38), Aydin (39), Atabey et al (40,41), Ercan et al (42),
Schumacher et al (43), and Le Pennec et al (44). After endemic mesothelioma in
the Cappadocia region was reported by Baris (45), Ataman (46,47), Mumpton (48),
Forster (49), Bish and Chipera (50), and Temel and Gundogdu (51) surveyed the
region and found zeolite-group minerals including erionite.
Previous medical studies of the area include those of Elmes (52,53), Pooley
(54,55), Sebastien et al (56,57), Rohl et al (58), Suzuki (59), and Ozesmi et al
(60,61).
Mesothelioma and Asbestos
Malignant pleural mesothelioma (MPM) is a relatively rare form of a lung cancer
in which thick layers of malignant cancer develop on the outer lining of the
lung. Regardless of the source of exposure (occupa¬tional or environmental) MPM
is a highly lethal disease, with the majority of patients dying within 6 to 18
months. Current therapy is unsatisfactory.
Malignant mesothelioma and exposure to different asbestos group minerals have
been studied by many, including McDonald and McDonald (62,63), Hillerdal and
Ozesmi (64), Kohyama (65), Leigh et al (66), De Klerk et al (67), Dogan and Emri
(68), and Gibbons (69). Between 1959 and 1977, approximately 4500 cases of
mesothelioma were diagnosed in the world by McDonald and McDonald (62). The
exposure to these carcinogenic materials could either be occupational or
environmental. Clinical, epidemiologic, and pathologic surveys and in vivo and
in vitro experimental work demonstrate that asbestos is responsible for the
etiology of mesothelioma.
Mesothelioma and Erionite
The interest in erionite, a fibrous form of a zeolite-group mineral, has grown
after the initial reports of a high incidence of malignant mesothelioma in the
villages of Karain and Tuzkoy in Cappadocian region of Turkey by Baris (45), and
later a village of Sarihidir by Baris et al (70). Baris et al (70), Ataman (48),
Artvinli and Baris (71), Ataman (47), Lilis (72), and Ozesmi et al (60,61)
studied the region and attempted to find a relationship between MPM and
erionite.
Mumpton (48) reported erionite in the villages where pleural mesothelioma
occurs. He also reported that erionite in other villages, such as Sarihidir,
reported no cases of mesothelioma. Therefore, he sug¬gested that some other
agent might be responsible for the high inci¬dence of mesothelioma in this
region. Baris et al (73) and Simonata et al (74) have shown that, contrary to
Mumpton (48), mesothelioma also occurred at unusually high rates in Sarihidir
village, Turkey.
Rohl et al (58) examined lung tissues and rock samples from this area. They
reported significant amounts of tremolite and chrysotile, in addi¬tion to
erionite. They concluded that their findings were consistent with the published
data, which showed a relationship between asbestos (chrysotile or amphibole)
exposure and pleural disease. Then they speculated on the existence of an
enhanced tumorigenic effect, which was probably produced by a combination of
asbestos and erionite. Sebastien et al (75) reported that the high frequency of
mesothelioma in the central Turkish villages was related to airborne exposure
from the natural mineral fibers. Wagner et al (76) examined the relationship
between erionite exposure and mesothelioma, using experimental studies on rats,
and found that samples of erionite from Turkey and Oregon produced a very high
incidence of mesothelioma.
Health effects of these mineral studies include those of Baris et al (73,77),
Casey et al (78,79), Sebastien et al (56,57), Artvinli and Baris (80), Maltoni
et al (81), Suzuki (59), Hillerdal and Baris (82), Sebastien et al (75),
Kruglikov et al (83), and Tatrai et al (84,85). Casey et al (78,79) reported
that fibrosis of the lung and pleura among workers was related to erionite but
not to asbestos. Several studies have been con¬ducted on the inhabitants of
“mesothelioma” villages in Turkey (with environmental exposure to erionite) and
on the inhabitants of control villages. Ferruginous bodies were found in a
higher proportion in the sputa of inhabitants of the contaminated villages than
in the control villages by Sebastien et al (75). Similarly, although not
statistically sig¬nificant, differences were found for pleural tissue changes by
Baris et al (77) and Artvinli and Baris (80) or pleural plaques by Baris et al
(73). Hillerdal and Baris (82) reported that pleural calcifications were more
frequent in inhabitants of erionite-exposed villages (78/549, 14.2%) and of
asbestos-exposed villages (104/446, 23.3%) than of control villages (3/382,
0.8%).
Carcinogeneity studies include those of Baris et al (70,73), Artvinli and Baris
(71), McDonald and McDonald (86), Boman et al (87), Artvinli and Baris (88),
Simonato et al (74), and Ozesmi et al (60). Most of the data on the
carcinogenicity of erionite in humans come from the expe¬rience of the
inhabitants of the erionite contaminated villages in Central Cappadocia, Turkey.
Baris et al (70) reported 25 cases of MPM in a pop¬ulation of 575 inhabitants of
Karain between 1970 and 1974; Baris et al (77) reported 28 MPMs in Karain
between 1975 and 1979; and Artvinli and Baris (88) examined over 25 years of 312
inhabitants of Tuzkoy between 1978 and 1980 and reported 15 MPMs, 12 malignant
peritoneal mesothelioma (MPeMs), and eight lung cancers. The incidence or
mor¬tality from mesothelioma was above 1%/year, a rate that is 10,000 times
higher than observed among populations nonoccupationally exposed to asbestos
from Western Europe or North America.
Baris et al (73) conducted an environmental and epidemiologic study in three
contaminated villages (Karain, Sarihidir, and Tuzkoy) and in one control village
(Karlik) in the period of 1979 to 1983. They reported that fibers taken from
street samples were 2–10, 5–25, 1–29, respectively for Karain, Sarihidir-Tuzkoy,
and Karlik; erionite amounts among fibers (>5mm) were 80%, 85%, 60%; numbers of
MPeM cases were
(males/females) 12/9, 0/5, 2/1; numbers of MPeM cases were (males/females) 0/0,
0/4, 0/0; numbers of lung cancer cases were (males/females) 2/0, 9/0, 5/1;
numbers of other cancers cases were (males/females) 20/11, 5/5, 13/4; and
numbers of other causes of death were (males/females) 15/17, 12/6, 13/17; Baris
et al (73) confirmed the high mortality from MPM and MPeM, and showed an excess
of lung cancer mortality in the contaminated villages. The young age of the
patients at the appearance of this respiratory neo¬plasm was particularly
noteworthy.
Boman et al (87) and Ozesmi et al (89) reported seven cases of mesothelioma
among about 100 men from one of the Cappadocian vil¬lages (Karain) who had
immigrated to Sweden. In this group, mesothe-lioma was the most common cause of
death, with an incidence of nearly 1%/year. Metintas et al (90) reported 14
deaths due to MPM among 162 Turkish emigrants from Karain who resided in Sweden.
In addi¬tion, there were five patients with mesothelioma (four MPM and one MPeM)
who were still alive. Thus it is calculated that the risk of mesothelioma for
men is 135 times and for the women it is 1336 times greater than for the same
sex and age groups in Sweden. The risk increased with time of residing in the
village. As in the studies from Turkey, mesotheliomas occurred at a young
average age. In subsequent analyses, a cumulative dose of 1 fiber/mL-year was
estimated to induce a pleural mesothelioma rate of 996 per 100,000 person-years
in the exposed population by Simonato et al (73).
Zeolite Toxicity Experiments Using Animals
Animal experimental studies include those of Suzuki and Kohyama (91), Wagner et
al (76), Pylev et al (92,93), Maltoni and Minardi (94), Davis et al (95), Tatrai
et al (84,85), and Carthew et al (96). Wagner et al (76) tested natural
erionite, synthetic nonfibrous zeolite with the composition of erionite and
crocidolite at concentrations of 10mg/m3 inhalation in rats. Pleural
mesotheliomas were found in 27/28 rats exposed to erionite; one pulmonary and
one pleural tumor were found in the 28 rats exposed to synthetic zeolite, and
one lung carcinoma was reported in rats exposed to crocidolite. A number of
experiments have been conducted on the intrapleural and intraperitoneal
administration of various types of erionite in mice and rats. These experiments
have all been positive, and showed a very high mesothelioma yield (90% or above)
for amounts of erionite above 0.5 or 1mg. For higher doses, the time of
appearance of the tumors was decreased (95,96). Other solid tumors, at the site
of inoculation, as well as lymphomas have been occa¬sionally described. Carthew
et al (96) compared the relative carcino¬genic potency of erionite and asbestos
fibers. In experiments based on intrapleural inoculation, erionite was 300 to
800 times more active than chrysotile, and 100 to 500 times more active than
crocidolite. In intraperitoneal experiments, erionite was 20 to 40 times more
active than chrysotile and 7 to 20 times more active than crocidolite.
Davis (97) showed that intrapleural injection of asbestos produced more tumors
than following intrapleural injection. Stanton et al (98) reported that the
tumorigenity of asbestos in relation to mesothelioma is attributable to fibers
longer than 8mm and less than 1.5mm in diam¬eter. Maltoni et al (81) tested
erionite and crocidolite fibers for car-cinogenicity. They reported pleural
mesothelioma after intrapleural injection with erionite fibers, but no pleural
tumors among the rats treated at the same time and in the same way with
crocidolite. Johnson et al (99) showed that tumors induced by asbestos and
erionite are mor¬phologically similar; however, the biologic activity of the two
mineral types was different. Suzuki and Kohyama (91) studied the effects of
intraperitoneal administration of mordenite and two natural erionites in mice.
They found that both erionites produced malignant peritoneal tumors at a high
rate, but mordenite did not produce any cancer. Wagner et al (76) showed that
the inhalation of erionite in comparison with asbestos produced tumors more
rapidly and more frequently.
Palekar et al (100) and Coffin et al (101,102), using both in vitro and in vivo
methods, demonstrated that erionite was much more tumori-genic than crocidolite
or chrysotile and induced chromosomal abnor¬malities. Coffin et al studied
mechanisms of tumorigenesis and tried to explain why erionite was more
tumorigenic than either crocidolite or chrysotile, in spite of the fact that
asbestos minerals typically have a far greater percentage of fibers in the
length-to-width class considered to be dangerous. They invoked the high internal
surface area of erion-ite (200m2/g) when compared with the total surface areas
for chrysotile (24m2/g) and crocidolite (8–10m2/g) as a possible reason for the
observed differences in tumorigenesis.
Mortality Studies
Clinical, epidemiologic, and pathologic surveys and in vivo and in vitro
experimental studies demonstrate that asbestos is responsible for the etiology
of mesothelioma. Epidemiologic and pathologic studies were carried out in South
Africa by Wagner et al (7); in the United Kingdom by Newhouse and Thomson (103);
in Germany by Bohlig et al (104); in Canada by McDonald et al (105); in France
by De Lajarte et al (106); in Australia by Milne (107); and in the United States
by Selikoff et al (108), Enterline (109), and Selikoff (110). These studies have
emphasized that approximately 70% to 85% of mesothelioma patients have been
exposed to asbestos through occupational, envi¬ronmental, or other means.
Three villages in Central Anatolia, Turkey, namely Tuzkoy, Karain, and
Sarihidir, comprise an extremely important field area and are infor¬mally
referred to as “the death triangle.” Since 1975, Baris has been investigating
this malignant mesothelioma in these three villages in Nevsehir, Turkey, and he
has maintained all patient records of this disease including chest x-rays and
personal health statistics. He also gathered the data on the death records of
patients who had died of
mesothelioma and other cancers in these villages in Turkey or abroad (i.e.,
Karain colony villagers in Sweden).
Epidemiologic records for these eight villages between the years 1994 and 1997
have been studied. An extremely high rate of cancer in the young-to-middle-age
group was observed in the study area. In vitro and in vivo studies performed by
the International Agency for Research on Cancer (IARC) and the World Health
Organization (WHO) also indicate that there is enough evidence to conclude that
these fibers are carcinogenic and that the cancer rate in this region is about
1000 times more than the normal rate.
Genetic Studies Suggest Predisposition to Erionite Carcinogenesis
Since erionite was elevated to the group status in 1997 there have been no
studies performed that quantitatively characterized erionite-Na, erionite-K, and
erionite-Ca in the various erionite villages. Thus we do not know to what types
of erionite these villagers are exposed. Family pedigree analyses conducted in
the village of Tuzkoy suggested that the carcinogenicity of erionite was more
pronounced in certain fami¬lies. Families with a high incidence of erionite were
identified, while in other families living in the same village the incidence of
mesothelioma was low. It did not appear that these differences could be
explained by different exposures to erionite since all villagers should be
exposed to similar amounts of erionite dust. Previous studies suggested that
eri-onite was carcinogenic at very low doses compared to asbestos (77). Thus,
the hypothesis of genetic predisposition to erionite carcino-genicity was
formulated (4,6). However, this hypothesis must be veri-fied in the other two
mesothelioma villages of Karain and “Old” Sarihidir. Moreover, the hypothesis
that mineralogic differences among houses within the same village is not
responsible for the different inci¬dence of mesothelioma among families in the
same village should also be verified by quantitative characterization of the
erionite found in these houses. It remains to be demonstrated that there are no
chemical differences among different houses in the same villages, or among
nearby villages, that could account for the different incidence of mesothelioma.
Our research team is investigating these possibilities.
Erionite in Turkey
Previous studies reported that erionite was found only in the three vil¬lages of
Karain, Sarihidir, Tuzkoy, and that the neighboring villages of Karacaoren (also
called Karacaviran) and Yesiloz (also called Tahar) were reported as
nonmesothelioma villages by Temel and Gundogdu (51). In contrast, our detailed
geologic and mineralogic study of the region showed that erionite is not
confined just to these three villages (111,112). In fact, the Karacaoren village
is also contaminated with erionite both in the bedrock and the wall rock.
Subsequent epidemiologic studies showed that the previously reported
nonmesothelioma villages such as
Karacaoren had a high rate of mesothelioma. Therefore, it was estab¬lished that
there was a direct relationship between erionite and nonoc-cupational malignant
mesothelioma in all of these villages in the region.
In Central Anatolia, Turkey, eruptions of volcanoes, mainly Erciyes (3917m) and
Hasandag (3268m), caused the region to be covered with a thick stratum of lava,
volcanic ashes, and a dense tuff layer that formed on the earth’s surface. In
the Cappadocian region, tuffs accu¬mulated in topographically low areas through
both direct airfall con¬tributions and the reworking of larger widespread ash
mantles. In time, natural factors such as rain and wind created extraordinary
shapes, deep valleys, and natural sculptures of fairy chimneys in the tuff
formations of this Cappadocian area. Single-tuff deposits consist of successive
accumulations of ash from more than one eruption event. Following deposition,
tuffs have undergone a series of geochemical changes involving an early
dissolution of glass surfaces and precipita¬tion of grain coating smectite,
followed by erionite growth in the pore spaces. A chemical environment of
increasing alkalinity is suggested to explain the observed mineralogic changes.
Activity diagrams of zeolites by Birsoy (113) also support this theory.
In the United States there are deposits of fibrous zeolites specifically in the
western portion of the country. There are homes made of zeolite (erionite) in
Oregon and weigh stations made of the same materials in Nevada. Very large
amounts of zeolites were also used in pozzolanic cements such as those used in
the construction of the Los Angeles aque¬duct in California. Recently, a few
cases of zeolite-related pulmonary diseases have been reported in the U.S.
Therefore, the possibility of increased exposure to zeolites in the western U.S.
is anticipated and potential carcinogenic dangers must be evaluated.
Erionite is the only zeolite whose evidence of carcinogeneity has been
evaluated. It is classified as a human carcinogen by the IARC (114). In Turkey,
erionite-contaminated villages in the Cappadocia region provide a natural
laboratory to study the health effect of these carcinogenic minerals, and the
villagers who immigrated from Karain to Sweden also form a unique community to
study the follow-up effects of zeolite exposure. The cancer rate in these
regions is about 1000 times higher than the normal rate. The local saying, “I
don’t know my father and my father doesn’t know his father,” indicates that the
cancer has been there for centuries.
This problem requires worldwide immediate attention. Although both the exposures
and biologic mechanisms are complex, we hope that the multidisciplinary medical
geology studies, which combine high-resolution mineralogy and human genetics,
will help us understand and control this very malignant human disease.
Conclusion
Mesothelioma, malignant pleural mesothelioma (MPM), or malignant peritoneal
mesothelioma (MPeM), is a very lethal disease. Clinical and experimental studies
have confirmed a carcinogenic linkage to
erionite, a zeolite-group mineral. In 1975 an extremely high rate of MPM
incidence was observed in some villages in the Cappadocian region of Turkey.
Further studies showed that the erionite type of zeolite minerals, not asbestos,
was the major cause of the epidemic in this area. The high potential of erionite
to induce MPM has been confirmed by both epidemiologic and experimental studies.
The World Health Organization (WHO) classified erionite, a zeolite group
mineral, as a group I carcinogen (114). The classification is based on evidence
in humans, specific diseases from occupational exposures, and health effects
noted in animal and cell experiments. Three types of erionite have been
described: erionite-Na, erionite-K, and erionite-Ca (10,11). Erionite is
observed in the previously reported villages and also in several new villages in
the Central Anatolian region of Turkey (111,112).
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