Hepatic macromolecular binding following exposure to vinyl chloride
Watanabe, P.G.; Zempel, J.A.; Pegg, D.G.; Gehring, P.J.
Toxicology and Applied Pharmacology 44(3): 571-579
1978
ISSN/ISBN: 0041-008X PMID: 684749 Document Number: 126628
Covalent binding of radioactivity to hepatic macromolecules in rats exposed to 14C-labeled vinyl chloride (VC) was studied to determine if VC-induced carcinogenesis may be related to electrophilic alkylation of macromolecules in vivo. Male Sprague-Dawley rats were exposed to 1, 10, 25, 50, 100, 250, 500 or 5000 ppm of [14C]VC for 6 h. Following exposure, radioactivity covalently bound to hepatic macromolecules and purified nucleic acids (RNA, DNA) was determined. The total amount of [14C]VC metabolized and hepatic glutathione (GSH) content were also determined. The total amount of radioactivity bound to macromolecules in the liver did not increase proportionately to the increase in the exposure concentration of VC. A disproportionate decrease in macromolecular binding was observed as the concentration of VC increased. Covalent binding to hepatic macromolecules was related to the amount of VC metabolized. At exposures greater than 50 ppm, the amount of 14C bound to macromolecules in the liver correlates with induction of hepatic angiosarcoma. There was no detectable binding of radioactivity to DNA or RNA in the liver. Hepatic glutathione content was significantly depressed only at exposure concentrations greater than 100 ppm.