Induction of tunica vaginalis mesotheliomas in rats by xenobiotics

To better understand the relevance of tunica vaginalis mesotheliomas (TVM) to human cancer risk, we examined the nature of TVM responses in 21 published rat cancer bioassays against the backdrop of the biology and molecular biology of mesothelium, and of spontaneous and treatment-induced TVM. Although relatively rare in all species including humans, TVM are seen most frequently in F344 male rats, as opposed to other rat strains, and are causally associated with the high background incidence of Leydig-cell tumors of the testes of these rats. Hormone imbalance brought about by perturbations of the endocrine system is proposed as a key factor leading to both spontaneous and treatment-associated TVM. Of 21 F344 rat studies with a treatment-associated TVM response, 7 were judged to have a nonsignificant to marginal response, 11 had a robust TVM response, and 3 were noninformative due to early mortality from other induced tumors. Of the 11 chemicals with robust responses, 8 were directly mutagenic in Salmonella...