Journal Article

Characterization by two-endpoint comparisons of the genetic toxicity profiles of vinyl chloride and related etheno-adduct forming carcinogens in <i>Drosophila</i>

L.A.P. Ballering, M.J.M. Nivard and E.W. Vogel

in Carcinogenesis

Volume 17, issue 5, pages 1083-1092
Published in print May 1996 | ISSN: 0143-3334
e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/17.5.1083
Characterization by two-endpoint comparisons of the genetic toxicity profiles of vinyl chloride and related etheno-adduct forming carcinogens in Drosophila

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The genetic toxicity profiles of vinyl chloride (VC1), vinyl bromide (VBr), ethyl carbamate (EC), vinyl carbamate (VC) and some structurally related chemicals were investigated in both somatic and germ cells of Drosophlia melanog-aster. In the white/white+ eye mosaic assay, a screening system measuring predominantly homologous recombination in somatic cells, only marginal genotoxic activities were observed for acetyl chloride (AC1), glycolaldehyde (GCA), 2,2′-dichlorodiethyl ether (DDE) and methyl carbamate (MC), whereas VC1, 2-chloroacetaldehyde (CAA), VBr, 2-bromoacetaldehyde (BAA) and EC were clearly recombinogenic in the assay. Those chemicals proven to be recombinogenic in somatic cells were investigated further in postmeiotic male germ cells, utilizing as descriptors of their genotoxicity ICL/RL and Mexr−/Mexr+ indices. The ICL/RL index is the rate of induced chromosome loss (CL), a clastogenic event, divided by the forward mutation rate, measured as recessive lethal (RL) mutations in 700 loci of the X-chromosome. The Mexr−/Mexr+ mutation enhancement ratio is obtained by determining RL under excision repair deficient versus repair proficient conditions. With ICL/RL values (2.7–6.9) similar to those obtained for cross-Unking agents, vinyl chloride, vinyl bromide, ethyl carbamate and vinyl carbamate are all efficient clastogenic agents in Drosophila germ cells. In the absence of excision repair, however, neither CEO nor CAA gave a hypermutability response (Mexr−/Mexr+ ≈1). By contrast, VC1, VBr, EC and VC showed clearly enhanced Mexr−/Mexr+ ratios, suggesting that these compounds produce some repairable DNA modifications) that are not generated by their epoxides. This unexpected finding points to the formation of other, yet unknown, metabolites of vinyl chloride, vinyl bromide, ethyl carbamate and vinyl carbamate. Our results support the concept that the epoxides chloroethylene oxide (CEO), bromoethylene oxide (BEO) and vinyl carbamate epoxide (VCO) are the most essential mutagenic intermediates. Compared to chloroethylene oxide (CEO), 2-chloroacetal-dehyde (CAA) was approximately 50 times less effective in the induction of RL, whereas BAA was inactive as a mutagen. These findings are consistent with the general view that CAA and BAA play no major role in the genotoxic action of vinyl halides.

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Subjects: Clinical Cytogenetics and Molecular Genetics

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