0000000000828061
AUTHOR
R. J. Laib
Alkylation of RNA by Vinyl Chloride and Vinyl Bromide Metabolites in Vivo: Effect on Protein Biosynthesis
Alkylation of DNA is viewed as representing the initial critical step in carcinogenesis induced by chemical substances. Vinyl chloride and vinyl bromide, compounds with proven carcinogenic potency toward the liver, are biotransformed to reactive metabolites which covalently bind to DNA (see Bolt et al. 1980). Furthermore, extensive covalent binding of metabolites of both vinyl chloride (Laib and Bolt 1977, 1978) and vinyl bromide (Ottenwalder et al. 1979) occurs to RNA of liver when rats are exposed to both vinyl halides. Defined products of alkylation are 1,N6-ethenoadenosine (Laib and Bolt 1777; Ottenwalder et al. 1979) and 3,N4-ethenocytidine (Laib and Bolt 1978; Ottenwalder et al. 1979)…
The rat liver foci bioassay: II. Investigations on the dose-dependent induction of ATPase-deficient foci by vinyl chloride at very low doses
In order to study the dose-dependence of the genotoxic effect of vinyl chloride (VC) hepatocellular ATPase-deficient foci were evaluated after subchronic exposure of newborn rats. Wistar rats were exposed from day 1 after birth over 10 weeks to 10, 40, 70, 150, 500 and 2000 p.p.m. VC (8 h/day; 5 days/week). One week after cessation of exposure hepatic ATPase-deficient foci were quantitated. For a subsequent investigation lower dose range groups of female and male Wistar and Sprague-Dawley rats were exposed (8 h/day; 5 days/week) to 2.5, 5, 10, 20, 40 and 80 p.p.m. VC. Exposure started at day 3 of life and lasted for 3 weeks. After cessation of exposure the animals were maintained for 10 wee…
The rat liver foci bioassay: I. Age-dependence of induction by vinyl chloride of ATPase-deficient foci
The age-dependence of the induction of pre-neoplastic enzyme-altered hepatic foci was investigated. Rats were exposed (8 h/day, 7 days/week) to 2000 p.p.m. vinyl chloride (VC) either 'transplacentally' (exposure of pregnant females), or immediately after birth for different time intervals (5, 11, 17, 47, 83 days) or from an age of 7 or 21 days onwards. The animals were then kept without further treatment; livers were evaluated for ATPase-deficient foci at the age of 4 months. 'Transplacental' exposure and exposure from day 1 through 5 caused no increase over controls in ATPase-deficient foci, probably due to the lack of hepatocellular proliferation and the low rate of VC metabolism at this …