Mutation induction in chinese hamster V79 cells by two vinyl chloride metabolites, chloroethylene oxide and 2‐chloroacetaldehyde

Huberman, Eliezer; Bartsch, Helmut; Sachs, Leo

doi:10.1002/ijc.2910160414

Cited by 76 publications

(17 citation statements)

References 21 publications

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“…Our observation of DNA SB by CAA is not unexpected as this compound is a strong mutagen [Huberman et al, 1975; McCann et al, 1975;Bartsch et al, 19761 and has been shown by several laboratories, including our own, to be highly DNA reactive [Barrio et al, 1975;Spengler and Singer, 1988, Kandala et al, 19901. The work presented here would suggest that the analog, DCAA, might also be a mutagen and form adducts with DNA.…”

Section: Discussionsupporting

confidence: 50%

Analysis of DNA strand breaks induced in rodent liver in vivo, hepatocytes in primary culture, and a human cell line by chlorinated acetic acids and chlorinated acetaldehydes

Chang

Daniel

DeAngelo

1992

Environ and Mol Mutagen

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An alkaline unwinding assay was used to quantitate the induction of DNA strand breaks (DNA SB) in the livers of rats and mice treated in vivo, in rodent hepatocytes in primary culture, and in CCRF-CEM cells, a human lymphoblastic leukemia cell line, following treatment with tri- (TCA), di- (DCA), and mono- (MCA) chloroacetic acid and their corresponding aldehydes, tri- (chloral hydrate, CH), di- (DCAA) and mono- (CAA) chloroacetaldehyde. None of the chloroacetic acids induced DNA SB in the livers of rats at 4 hr following a single administration of 1-10 mmole/kg. TCA (10 mmole/kg) and DCA (5 and 10 mmole/kg) did produce a small amount of strand breakage in mice (7% at 4 hr) but not at 1 hr. N-nitrosodiethylamine (DENA), an established alkylating agent and a rodent hepatocarcinogen, produced DNA SB in the livers of both species. TCA, DCA, and MCA also failed to induce DNA strand breaks in splenocytes and epithelial cells derived from the stomach and duodenum of mice treated in vivo. None of the three chloroacetaldehydes induced DNA SB in either mouse or rat liver. The continuous exposure of mice to 5 g/L DCA in the drinking water for 7 and 14 days did not induce appreciable hepatic DNA SB (< 10% at 14 days), although peroxisome proliferation, as evidenced by an increased cyanide-insensitive palmitoyl CoA oxidase (PCO) activity, was stimulated to 490% (7 days) and 652% (14 days) of control. Under this protocol, DENA (0.1 g/L) produced DNA damage after both 7 days (73% of control) and 14 days (57% of control). Similarly, long-term exposure of rats (30 weeks) to 2 g/L DCA in the drinking water, a level that increased PCO activity to 364% of the control value, exhibited no DNA damage. Both the chloroacetic acids and the chloroacetaldehydes were ineffective in inducing DNA SB in cultured rat and mouse hepatocytes at concentrations below those that yielded cytotoxicity. The chloroacetic acids were also ineffective in the CCRF-CEM cells. However, two of the chloroaldehydes, DCAA and CAA, did induce DNA SB in the CCRF-CEM cells at concentrations that did not decrease the cell viability after 2 hr of treatment. Prior incubation of DCAA and CAA with a rat S9 liver homogenate eliminated much of the DNA damaging activity. These studies provide further evidence that the chloroacetic acids lack genotoxic activity not only in rodent liver, a tissue in that they induce tumors, but in a variety of other roden tissues and cultured cell types.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Discussionsupporting

confidence: 50%

Analysis of DNA strand breaks induced in rodent liver in vivo, hepatocytes in primary culture, and a human cell line by chlorinated acetic acids and chlorinated acetaldehydes

Chang

Daniel

DeAngelo

1992

Environ and Mol Mutagen

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“…Similar results were obtained by Huberman et al (6) in Chinese hamster V-79-4 cells: a dose-dependent induction of 8-azaguanine-or oubain-resistant mutants was observed with chloroethylene oxide, where as 2-chloroacetaldehyde induced only 8-azaguanine-resistant mutants and resulted in a high cytoxicity. 2-Chloroethanol and monochloroacetic acid were inactive even at concentrations up to 100 times as high.…”

Section: Mutagenicitysupporting

confidence: 88%

Mutagenicity and Metabolism of Vinyl Chloride and Related Compounds

Bartsch¹,

Malaveille²,

Barbin³

et al. 1976

Environmental Health Perspectives

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The various adverse biological effects of vinyl chloride appear to be dependent upon the metabolic conversion of this compound into chemically reactive metabolites. The metabolism of vinyl chloride in mammals and in man, including the formation of monochloroacetic acid and some identified sulfur conjugates is reviewed. Hepatic microsomal mixed function oxidases from rats, mice, and humans were equally effective in transforming vinyl chloride into alkylating agents in vitro. Two of the enzyme reaction products, i.e., chloroethylene oxide and 2-chloroacetaldehyde, showed potent genetic activity in microorganisms and Chinese hamster V79 cells. The role of liver microsomal enzymes in the generation of electrophilic mutagenic vinyl chloride metabolites is discussed.Chlorinated hydrocarbons, such as vinyl chloride (VCM) or vinylidene chloride, are widely used in the production of plastic resins and are present in the environment (1, 2). It is now recognized that VCM is responsible for various adverse biological effects which induce neoplastic and nonneoplastic diseases in man as well as in animals (2) and that these effects seem to be attributable not to VCM itself but to reactive metabolites formed by microsomal mixed-function oxidases. Many chemical carcinogens have been shown to exert a carcinogenic effect following their metabolic activation into elctrophilic metabolites which react readily with cellular macromolecules (3). This paper is a review of results obtained in our laboratory and by others concerning the mutagenicity of VCM and related compounds and the metabolism of some of these compounds. MutagenicityThe mutagenicity of VCM has been examined in various strains of S. typhimurium in which

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“…The inactivity of chloroacetaldehyde AIBEHYDES IN CARCINOGENESIS 241 was a rather surprising result, as chloroacetaldehyde is mutagenic In bacteria (83), Chinese hamster V-79 cells (84), and is strongly implicated as the proximal carcinogen formed from vinyl chloride. Bartsch and coworkers found the same result; in their study chloroethylene oxide and bis-(chloromethyl)ether were carcinogenic in mice, but chloroacetaldehyde was not (85).…”

Section: Chloroacetaldehydementioning

confidence: 96%

Role of aldehydes in carcinogenesis

Goldschmidt

1984

Journal of Environmental Science and Health. Part C: Environmen

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Mutation induction in chinese hamster V79 cells by two vinyl chloride metabolites, chloroethylene oxide and 2‐chloroacetaldehyde

Cited by 76 publications

References 21 publications

Analysis of DNA strand breaks induced in rodent liver in vivo, hepatocytes in primary culture, and a human cell line by chlorinated acetic acids and chlorinated acetaldehydes

Analysis of DNA strand breaks induced in rodent liver in vivo, hepatocytes in primary culture, and a human cell line by chlorinated acetic acids and chlorinated acetaldehydes

Mutagenicity and Metabolism of Vinyl Chloride and Related Compounds

Role of aldehydes in carcinogenesis

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