title: Rat liver foci and in vitro assays to detect initiating and promoting effects of chlorinated ethanes and ethylenes.
abstract: Nine chlorinated aliphatics (CAs) were examined in a rat liver foci assay for tumor initiating and promoting activities. In this model, young adult male Osborne Mendel rats were first subjected to a partial hepatectomy, the test chemical was then administered at the maximum tolerated dose in the initiation or promotion phase in conjunction with diethylnitrosamine (DEN; 30 mg/kg b.w.) or phenobarbital (PB; 0.05 percent, w/w, in the diet), and gamma glutamyltranspeptidase (GGT) was used as a putative preneoplastic indicator. When administered in the promotion protocol after initiation with DEN, 1,1-dichloroethane, 1,1,2-trichloroethane (1,1,2-TCE), 1,1,2,2-tetrachloroethane (1,1,2,2-TTCE), tetrachloroethylene (TTCY), and hexachloroethane induced significant increases in GGT+-foci above control levels. 1,1,2,2-TTCE, TTCY, and 1,1,2-TCE also induced significant increases in GGT+-foci when administered in the promotion protocol without DEN initiation. Two variants of GGT+-foci were observed: the classical type associated with PB promotion, and the other, which was more diffuse, less intensely stained, resembling foci undergoing redifferentiation and associated with CAs. A number of CAs were also genotoxic in short-term in vitro tests. Taken together, the studies suggest that CAs may be complete carcinogens in vivo with weak initiating activity and stronger promoting activity.
authors.affiliation: Office of Pesticides and Toxic Substances, U.S. Environmental Protection Agency, Washington, D.C. 20460.
authors.forename: H A
authors.initials: HA
authors.lastname: Milman
authors.forename: D L
authors.initials: DL
authors.lastname: Story
authors.forename: E S
authors.initials: ES
authors.lastname: Riccio
authors.forename: A
authors.initials: A
authors.lastname: Sivak
authors.forename: A S
authors.initials: AS
authors.lastname: Tu
authors.forename: G M
authors.initials: GM
authors.lastname: Williams
authors.forename: C
authors.initials: C
authors.lastname: Tong
authors.forename: C A
authors.initials: CA
authors.lastname: Tyson
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D004980:Ethane / Q000031:analogs & derivatives* / Q000633:toxicity; D005025:Ethylene Dichlorides / Q000633:toxicity*; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D008099:Liver / Q000187:drug effects*; D008297:Male; D051379:Mice; D009152:Mutagenicity Tests; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D013750:Tetrachloroethylene / Q000633:toxicity*; D014240:Trichloroethanes / Q000633:toxicity*
chemical_list: D005025:Ethylene Dichlorides; D006843:Hydrocarbons, Chlorinated; D014240:Trichloroethanes; C015530:1,1,2,2-tetrachloroethane; C024567:1,1,2-trichloroethane; C010182:hexachloroethane; D004980:Ethane; D013750:Tetrachloroethylene