Activity of the anorectic agent 1,3-bis[2-cyano-5-(trifluoromethyl)-phenyl]triazene in in vitro and in vivo liver promoting assays.
A substituted 1,3-diaryltriazene, 1,3-bis[2-cyano-5-(trifluoromethyl)phenyl]triazene (BPT), was studied for promoting activity in vitro and in vivo. BPT inhibited intercellular molecular exchange between cultured hepatocytes and rat liver epithelial cells, although the effect was not consistent. For the in vivo assay, male F344 rats were first exposed to N-2-fluorenylacetamide (FAA) for 8 weeks to induce liver altered foci, after which those maintained on control diet for an additional 12 weeks developed a 33% incidence of liver neoplasms. In rats given 0.02% BPT in the diet as a second exposure, the final incidence of liver neoplasms was 92%, which was comparable to the enhancement by phenobarbital (PB), a known liver neoplasm promoter. In the rats given BPT after FAA, the area occupied by gamma-glutamyltranspeptidase (GGT)-positive preneoplastic and neoplastic lesions was significantly higher than in the rats exposed to FAA only. Feeding of BPT alone for 12 weeks did not induce either liver altered foci or neoplasms and it was non-genotoxic in the hepatocyte DNA repair test. Therefore, although additional studies are needed to firmly establish the basis for the enhancement of liver carcinogenesis, BPT is suggested to be a new type of liver neoplasm promoter.
Maruyama
H
H
American Health Foundation, Valhalla, NY 10595.
Tanaka
T
T
Williams
G M
GM
D015073:2-Acetylaminofluorene / Q000633:toxicity; D000284:Administration, Oral; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002450:Cell Communication / Q000187:drug effects; D003043:Cocarcinogenesis; D004260:DNA Repair / Q000187:drug effects; D004357:Drug Synergism; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D014226:Triazenes / Q000494:pharmacology / Q000633:toxicity*
D002273:Carcinogens; D014226:Triazenes; C038160:1,3-bis(2-cyano-5-(trifluoromethyl)phenyl)triazene; D015073:2-Acetylaminofluorene