In vitro cytological and cytogenetic effects of an Indian variety of chrysotile asbestos

Ka, Babu; Bc, Lakkad; Sk, Nigam; Dk, Bhatt; Ab, Karnik; Kn, Thakore; Sk, Kashyap; Sk, Chatterjee

doi:10.1016/0013-9351(80)90045-6

Cited by 27 publications

(1 citation statement)

References 7 publications

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“…On the other hand, it has been argued that asbestos may not act as an initiator, since it lacks mutagenic activity, a property of most initiators. Although asbestos is not active as a gene mutagen in a variety of test systems, there is now clear evidence that it induces chromosomal mutations (aneuploidy and aberrations) in a wide variety of mammalian cells, including mesothelial cells [Jaurand, 1986[Jaurand, , 1989Chamberlain and Tarmy, 1977;Barrett, 1987;Oshimura et al, 1984;Sincock and Seabright, 1975;Babu et al, 1980;Valerio et al, 1980;Lavappaet al, 1975;Lechner et al, 1985a,b;Linnainmaa et al, 19861. Finally, it has been shown that asbestos can induce transformation of cells in culture, including mesothelial cells and fibroblasts [Lechner et al, 198s'a;Hesterberg and Barrett, 1984;Hesterberg et al, , 1986Paterour et al, 1985a,b].…”

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confidence: 98%

Possible cellular and molecular mechanisms for asbestos carcinogenicity

Walker

Everitt

Barrett

1992

American J Industrial Med

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Asbestos fibers may exert their carcinogenic effects on mesothelial cells and bronchial epithelial cells by direct and indirect mechanisms. Direct effects can occur following the physical interaction of fibers with target cells or by the generation of free radicals from the fiber surface; indirect effects, following the interaction of fibers with inflammatory cells can result in the production of cellular mediators such as cytokines and various reactive oxygen species. As a result, target cells may be induced to proliferate and/or sustain genetic alterations, which lead to tumor development.

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mentioning

confidence: 98%

Possible cellular and molecular mechanisms for asbestos carcinogenicity

Walker

Everitt

Barrett

1992

American J Industrial Med

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Implications of multiple mechanisms of carcinogenesis for short‐term testing

Harper¹,

Morris

1984

Teratog Carcinog Mutagen

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The attempt has been made recently to categorize carcinogens into two mechanistic types based on their mechanism of action: genotoxic (capable of reacting with and damaging DNA) and epigenetic (unable to damage DNA to any detectable extent). By requiring that a given chemical fit into one or the other of these narrowly defined categories for regulatory purposes, we are probably oversimplifying potential biological effects. In fact, based on our limited understanding of carcinogenic mechanisms, this artificial distinction should probably be abandoned in favor of a more precise statement of each chemical's mechanism or relative potency of initiating and promoting effects. Since the standard short-term tests by which carcinogenicity of chemicals is screened were designed to detect certain chemical classes with active electrophilic intermediates, weak or specialized carcinogens may be missed and may be assumed erroneously to be nongenotoxic. The mechanisms of carcinogenicity for such carcinogens may include particulate deposition, active radical formation, liver toxicity, and hormonal interactions. Not all of these secondary mechanisms depend upon a detectable level of binding to DNA, damage to DNA, or modification of the DNA sequence, even though they may demonstrate other characteristics of a complete carcinogen (that is, irreversibility and lack of a threshold). Certain agents have been labeled as epigenetic. However, a consideration of the literature on sample agents (diethylstilbestrol, asbestos, and urethane) reveals that these are not epigenetic carcinogens despite their being labeled as such. Agents with irreversibility and no threshold have initiating potential and, as such, are genotoxic, whereas carcinogens that are classified as nongenotoxic are largely agents that promote the growth of liver tumors. Even promotion can be a mechanistically specialized phenomenon. For example, some promoters are cytotoxic to the liver, but not all liver toxins are liver tumor promoters or liver carcinogens. Further, the carcinogens commonly labeled as epigenetic might cause a unique specialized genotoxicity not detected by common screening tests routinely used for detecting genotoxicity. If we assume that this unrecognized but necessary initiating potential is mediated by some specialized genotoxicity, extra care must be taken to establish a genuine lack of genotoxicity before an agent can be classified (and regulated) as a promoter (lacking the ability to initiate tumor growth but still enhancing tumor development).(ABSTRACT TRUNCATED AT 400 WORDS)

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