Nine chlorinated aliphatics (CAs)—1,1-dichloroethane, 1,2-dichloro ethane, 1,1,1-trichloroethane, 1,1,2-trichloroethane, trichloro ethylene, tetrachloroethylene, 1,1,1,2-tetrachloroethane, 1,1,2,2- tetrachloroethane, and hexachloroethane—were examined in a rat liver foci assay for evidence of initiating and promoting potential. Young adult male Osborne-Mendel rats (ten/group) were given partial hepa tectomies, followed 24 hr later by a single i.p. dose of either diethyl nitrosamine (30 mg/kg body weight) or CA, 1 wk later either a diet containing 0.05% (w/w) phenobarbital or daily oral gavage (5 × /wk) of CA in corn oil for 7 weeks, and sacrificed 1 wk later. Putative preneo plastic markers monitored were foci with increased γ-glutamyltrans peptidase activity [GGT( + )]. CAs were without significant effect in the initiation protocol at the maximum tolerated dose. In the promotion protocol, 1,1-dichloroethane, 1,1,2-trichloroethane, tetrachloro ethylene, 1,1,2,2-tetrachloroethane, and hexachloroethane induced significant increases in GGT( + ) foci above control levels. Two variants of GGT( + ) foci were distinguishable, one associated predominantly with phenobarbital promotion, resembling preneoplastic foci in other models, and the other associated with CA promotion, which was less intensely stained and exhibited branching, resemblingfoci undergoing redifferentiation. The marked differences in response may relate to differences in cytotoxic potential or mechanism of action of the two types of agents.
Suppression of Diethylnitrosamine-initiated Preneoplastic Foci Development in the Rat Liver by Combined Administration of Four Antioxidants at Low Doses