Covalent Binding of the Carcinogen Trichloroethylene to Hepatic Microsomal Proteins and to Exogenous DNA in V/fro1

Studies were carried out on the in vitro covalent binding of the carcinogen trichloroethylene (TCE) to liver microsomal preparations and to exogenous DNA. The binding of TCE to liver microsomal proteins of male C57BL/6 x C3H/He F, (hereafter called B6C3F ) hybrid mice, a spe cies and strain susceptible to TCE-induced liver tumorigenesis, was 46% higher than that of [' 'C]TCE to micro somal proteins from male Osborne-Mendel rats, a species and strain resistant to TCE-induced hepatocellular carci noma. The in vitro binding of [ 4C]TCEto liver microsomal proteins was 37% higher for male B6C3F, mice; female B6C3F, mice that have been reported to show a lower incidence of TCE-induced hepatocellular carcinoma than do males. Microsomal proteins from the lung, stomach, and kidney of B6C3F hybrid mice also metabolized TCE, as indicated by the covalent binding of [14C]TCEto micro somal proteins from these organs. For rats the binding of TCE to liver microsomal proteins of Sprague-Dawley ani mals was higher than that of Osborne-Mendel and Fischer 344 rats. Incubation of [14C]TCEwith salmon sperm DNA in the presence of microsomal preparations from B6C3F, hybrid mice resulted in covalent binding of [14C]TCE to DNA. This binding was much higher in the presence of microsomal proteins from male rather than female mice. The binding to DNA and protein was enhanced by in vivo phénobarbitaladministration. The effects of 1,2-epoxy3,3,3-trichloropropane on the covalent binding of [ 'C]TCE to protein and DNA were also examined.