Benzene induces a dose-responsive increase in the frequency of micronucleated cells in rat Zymbal glands.

The Zymbal gland, a sebaceous tissue associated with the ear duct of certain rodent species, is a principal target for carcinogenesis by benzene. To investigate the mechanism of induction of tumors in the rat Zymbal gland, we have developed a procedure for primary culture of epithelial cells from Zymbal gland explants so that cytogenetic analysis can be performed on this target tissue following an in vivo exposure to benzene. Cytogenetic analysis performed 45 hr after in vivo oral dosing with benzene revealed chromosome damage that occurred as a result of acute, subchronic, and chronic dosing. This damage, expressed as a dose-related increase in the frequency of micronucleated cells, was observed in Sprague-Dawley female rats over a range of benzene doses from 12.5 to 250 mg/kg/day, and in male Fischer 344 rats at doses ranging from 1 to 200 mg/kg/day. These results are consistent with the known clastogenicity of benzene in mouse bone marrow, which is also a target tissue. This study is the first report of a genotoxic effect of benzene in the rat Zymbal gland and shows that micronucleus formation may be used as a correlate for carcinogenesis induced by benzene in this target tissue.