Abstract
[1,2-14C]Vinyl bromide was incubated with rat liver microsomes, NADPH, and polyadenylic acid, polycytidylic acid, or RNA, respectively. Part of the adenosine moieties in RNA or in polyadenylic acid were alkylated and labelled 1,N6-ethenoadenosine structures were formed. Part of the cytidine moieties were converted into 3,N4-ethenocytidine. In addition, a further unidentified cytidine alkylation product was observed which was not seen in experiments using [1,2-14C]vinyl chloride. When rats were exposed to [1,2-14C]vinyl bromide, radioactive ethenoadenosine and ethenocytidine were present in hydrolysates of liver RNA. A further alkylation product was observed in the RNA hydrolysates which did not occur in experiments using [14C]vinyl chloride. The data show that vinyl bromide metabolites alkylate nucleic acids; although in general in this respect vinyl bromide and vinyl chloride behave similarly, some differences are observed in the alkylation behaviour of both compounds.
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Anonymous: Vinyl bromide tests show increase in cancer in rats. Chemical Week, Nov. 16, p. 40 (1977)
Barbin, A., Brésil, H., Croisy, A., Jacquignon, P., Malaveille, C., Montesano, R., Bartsch, H.: Livermicrosome-mediated formation of alkylating agents from vinyl bromide and vinyl chloride. Biochem. Biophys. Res. Commun. 67, 596–603 (1975)
Bolt, H. M., Remmer, H.: Implication of rifampicin-quinone in the irreversible binding of rifampicin to macromolecules. Xenobiotica 6, 21–32 (1976)
Bolt, H. M., Kappus, H., Buchter, A., Bolt, W.: Disposition of 1,2-14C-vinyl chloride in the rat. Arch. Toxicol. (Berl.) 35, 153–162 (1976)
Bolt, H. M., Filser, J. G., Hinderer, R. K.: Rat liver microsomal uptake and irreversible protein binding of 1,2-14C-vinyl bromide. Toxicol. Appl. Pharmacol. 44, 481–489 (1978)
Conolly, R. B., Jaeger, R. J., Szabo, S.: Acute hepatotoxicity of ethylene, vinyl fluoride, vinyl chloride, and vinyl bromide after arochlor 1254 pretreatment. Exp. Mol. Pathol. 28, 25–33 (1978)
Drew, R. T., Patel, J. M., Van Stee, E. W.: The effects of vinyl bromide exposure in rats pretreated with phenobarbital or diethylmaleate. Toxicol. Appl. Pharmacol. 37, 176–177 (1976)
Georgiev, G. P., Mantieva, V. L.: The isolation of DNA-like RNA from the nucleo-chromosomal apparatus of mammalian cells. Biochim. Biophys. Acta 61, 153–154 (1962)
Kappus, H., Bolt, H. M., Buchter, A., Bolt, W.: Liver microsomal uptake of 14C-vinyl chloride and transformation to protein alkylating metabolites in vitro. Toxicol. Appl. Pharmacol. 37, 461–471 (1976)
Laib, R. J., Bolt, H. M.: Alkylation of RNA by vinyl chloride metabolites in vitro and in vivo: Formation of 1,N6-ethenoadenosine. Toxicology 8, 185–195 (1977)
Laib, R. J., Bolt, H. M.: Formation of 3,N4-ethenocytidine moieties in RNA by vinyl chloride metabolites in vitro and in vivo. Arch. Toxicol. (Berl.) 39, 235–240 (1978)
Laib, R. J., Bolt, H. M., Buchter, A., Kappus, H., Bolt, W.: Untersuchungen zur Toxikologie von Vinylchlorid. Verh. Dtsch. Ges. Arbeitsmedizin 17, 243–250 (1977)
Murphy, S. D.: Conference on comparative metabolism and toxicity of vinyl chloride-related compounds: Overview and summary. Environ. Health Perspect. 21, 327–328 (1977)
Scherrer, K., Darnell, J. E.: Sedimentation characteristics of partly labelled RNA from Hela cells. Biochem. Biophys. Res. Commun. 7, 486–490 (1962)
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Ottenwälder, H., Laib, R.J. & Bolt, H.M. Alkylation of RNA by vinyl bromide metabolites in vitro and in vivo. Arch. Toxicol. 41, 279–286 (1979). https://doi.org/10.1007/BF00296897
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DOI: https://doi.org/10.1007/BF00296897