Tumour Promotion Related Effects by the Cyclodiene Insecticide Endosulfan Studied <i>in Vitro</i> and <i>in Vivo</i>

Abstract

The cyclodiene insecticide endosulfan is structurally related to the tumour promoting pesticides chlordane and heptachlor. Divergent conclusions have been reported regarding the carcinogenic activity of endosulfan. In this study we have investigated if endosulfan and four of its metabolites possess tumour promotion related effects. Two in vitro test systems detecting inhibition of intercellular communication were used; the Chinese hamster lung fibroblast (V79) metabolic cooperation assay and a scrape loading/dye transfer assay using rat liver WB epithelial cells. At non-cytotoxic concentrations, technical grade endosulfan, analytical grade endosulfan (alpha- and beta-isomers and an alpha beta-isomer mixture) and endosulfan-sulfate inhibited gap junctional communication in both assay systems. In addition, the metabolite endosulfan-ether was effective in the rat liver WB epithelial cells. Endosulfan was also studied for enhancement of gamma-glutamyl transpeptidase positive enzyme altered foci incidence in partially hepatectomized, nitrosodiethylamine-initiated male Sprague-Dawley rats. However, endosulfan administered orally (1 or 5 mg/kg/day) five days a week for ten weeks did not enhance enzyme altered foci incidence. These apparently contradictory results with regard to possible tumour promoting activity of endosulfan are discussed in relation to metabolism, systemic toxicity and tissue/species specificity in tumour promotion.