Carcinogenicity studies on fibres, metal compounds, and some other dusts in rats

Pott, F.; Ziem, Ursula; Reiffer, Franz Josef; Huth, Felix; Ernst, Heinrich; Möhr, U.

doi:10.1016/s0232-1513(87)80044-0

Cited by 255 publications

(143 citation statements)

References 32 publications

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“…Autopsies demonstrated the occurrence of peritoneal lesions such as adhesions and tumours in mice exposed to crocidolite, but not in saline controls, in agreement with previous results obtained in asbestos-treated rodents (Suzuki and Koyama, 1984;Pott et al, 1987;Smith et al, 1987;Davis et al, 1991;Roller et al, 1996). In asbestos-treated mice, peritoneal nodules (16% in WT and 14% in Nf2 KO3/ þ mice) were observed mostly in association with adhesions (87.5% in WT and 88% in Nf2 KO3/ þ mice).…”

Section: Resultssupporting

confidence: 91%

Hemizygosity of Nf2 is associated with increased susceptibility to asbestos-induced peritoneal tumours

et al. 2003

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Biallelic NF2 gene inactivation is frequently found in human malignant mesothelioma. In order to assess whether NF2 hemizygosity may enhance susceptibility to asbestos fibres, we investigated the Nf2 status in mesothelioma developed in mice presenting a heterozygous mutation of the Nf2 gene (Nf2 KO3/ þ ), after intraperitoneal inoculation of crocidolite fibres. Asbestos-exposed Nf2 KO3/ þ mice developed tumoural ascites and mesothelioma at a higher frequency than their wild-type (WT) counterparts (Po0.05). Six out of seven mesothelioma cell lines established from neoplastic ascitic fluids of Nf2 KO3/ þ mice exhibited loss of the WT Nf2 allele and no neurofibromatosis type 2 protein expression was found in these cells. The results show the importance of the NF2 gene in mesothelial oncogenesis, the potential association of asbestos exposure and tumour suppressor gene inactivation, and suggest that NF2 gene mutation may be a susceptibility factor to asbestos.

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Section: Resultssupporting

confidence: 91%

Hemizygosity of Nf2 is associated with increased susceptibility to asbestos-induced peritoneal tumours

et al. 2003

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“…Many studies have demonstrated that fiber length and durability were determinant in fiber-induced carcinogenesis (1)(2)(3). Epidemiological studies of tumor frequency in workers exposed to airborne asbestos or MMMF neither confirm nor refute that conclusion.…”

Section: Introductionmentioning

confidence: 99%

Solubility of chrysotile asbestos and basalt fibers in relation to their fibrogenic and carcinogenic action.

Kogan

Нікітіна

1994

Environ Health Perspect

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Fiber length and persistence are thought to be determinants for the development of toxic, fibrogenic, and carcinogenic effects of fibrous dusts.When the solubilities of chrysotile asbestos (CA) and basalt fibers (BF) were compared by measuring the loss of silica and magnesium in Leineweber's solution, CA was shown to be the more soluble. In a 6-month inhalation experiment, chrysotile at a mean concentration of 25 mg/m3 had a higher clearance rate than other comparable dusts. In acute toxicity studies, chrysotile and basalt fibers were administered intraperitoneally. At a dose of 1.7 g/kg body weight of CA, one third of the animals died. A dose of 2.7 g/kg body weight killed all the animals. With BF, even at a dose of 10 g/kg body weight all the animals survived. When the two fibers were administered over a 6-month period, either intratracheally or by inhalation, fibrotic lesions were more common in the group that received CA. Intraperitoneal administration of CA led to three times as many deaths from peritoneal mesothelioma as administration of BF. It appears, therefore, that in spite of its higher solubility and lower persistence, CA was the more toxic, fibrogenic, and carcinogenic fiber, which gives rise to the hypothesis that the surface chemistry of the fibers is the determinant for biological activity.

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“…In addition, we have used our challenge assay to elucidate cytogenetically its effects on DNA repair. We have chosen to study nickel acetate because it is a soluble carcinogenic compound (27)(28)(29)(30) and its clastogenic effects have not been adequately investigated.…”

Section: Introductionmentioning

confidence: 99%

Toxicological interactions between nickel and radiation on chromosome damage and repair.

Heo²,

Chiewchanwit³

1994

Environ Health Perspect

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Carcinogenic nickel compounds are usually found to be weak mutagens; therefore these compounds may not exert their carcinogenic activity through conventional genotoxic mechanisms. On the other hand, the activities of many nickel compounds have not been adequately investigated. We evaluated the genotoxic activities of nickel acetate using conventional chromosome aberration and sister chromatid exchange assays and found that there was no increase of chromosome aberrations or sister chromatid exchanges, although the highest dose (1000 pM) caused mitotic inhibition. In addition,. we investigated its effect on DNA repair using our challenge assay. In this assay, lymphocytes were exposed to 0.1 to 100 pM nickel acetate for 1 hr during the GO phase of the cell cycle. The cells were washed free of the chemical and, 1.5 hr later, were irradiated with two doses of y-rays (75 cGy per dose separated by 60 min). A significant dose-dependent increase of chromosome translocations was observed (p<0.05). The increase is more than expected based on additive effects from exposure to nickel or trays individually. In contrast to the increase of chromosome translocations, there was no increase in chromosome deletions, although there was a nickel dose-dependent reduction of mitotic indices. Our data suggest that pretreatment with nickel interferes with the repair of radiation-induced DNA damage and potentially cause mistakes in DNA repair. Furthermore, we suggest that nickel-induced abnormal DNA repair may be a mechanism for its carcinogenic properties. The DNA repair problems that we observed after exposure to low doses of nickel may be viewed as a type of adaptive response. Contrary to some investigators who showed that adaptive responses may be beneficial, our data indicated that some responses may cause more problems than expected.-Environ Health Perspect 102(Suppl 9): 73-77 (1994)

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Carcinogenicity studies on fibres, metal compounds, and some other dusts in rats

Cited by 255 publications

References 32 publications

Hemizygosity of Nf2 is associated with increased susceptibility to asbestos-induced peritoneal tumours

Hemizygosity of Nf2 is associated with increased susceptibility to asbestos-induced peritoneal tumours

Solubility of chrysotile asbestos and basalt fibers in relation to their fibrogenic and carcinogenic action.

Toxicological interactions between nickel and radiation on chromosome damage and repair.

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