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© 1992 Oxford University Press

research-article

The insecticide endosulfan and its two stereoisomers promote the growth of altered hepatic foci in rats

Ronny Fransson-Steen 1 2 3, Sten Flodström 1 and Lars Wärngard 1

1Institute of Environmental Medicine, Karolinska Institutet Box 60208, S-104 01 Stockholm
2Department of Toxicology, Karolinska Institutet Box 60400, S-104 01 Stockholm, Sweden

3To whom correspondence should be addressed

The non-genotoxic, chlorinated cyclodiene insecticide endosulfan was studied for its ability to act as a tumour promoter in a two-stage, altered hepatic foci bioassay in male Sprague-Dawley rats. Two stereoisomers of endosulfan, {alpha}-endosulfan (ENDO{alpha}) and ß-endosulfan (ENDOß3) were used, as well as a commercially-occurring mixture of the {alpha}-and ß-isomers (ENDO{alpha}ß). The animals were initiated by intraperitoneal injection of nitrosodiethylamine 24 h after a two-thirds-partial hepatectomy. Five weeks later the animals were transferred to diets containing 30, 100 and 300 p.p.m. of either ENDO{alpha}ß, END{alpha} or ENDOß. The study was terminated 25 weeks after initiation and the development of foci of {gamma}-glutamyltranspeptidase-positive hepatocytes was evaluated by stereological methods. The results show that endosulfan and its two stereoisomers promote the development of altered hepatic foci, suggesting that endosulfan is a tumour-promoting agent acting by clonal expansion of initiated cells.


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