MODIFICATION OF THE CARCINOGENIC POTENCY OF QUINOLINE, A HEPATOCARCINOGEN, BY FLUORINE ATOM SUBSTITUTION - EVALUATION OF CARCINOGENICITY BYA MEDIUM-TERM ASSAY

The potent mutagen, 5-fluoroquinoline (5-FQ), and non-mutagenic 3-fluo roquinoline (3-FQ) mere tested for hepatocarcinogenicity using a mediu m-term assay system employing quinoline, a moderately mutagenic hepato carcinogen, as a reference. F344 male rats were given a single i.p. in jection of a submanifestational dose of diethylnitrosamine (DEN, 200 m g/kg), Then, quinoline, 3-FQ, or 5-FQ at two doses (0.1% and 0.05%) wa s added to their diet for a period of 6 weeks, starting from 2 weeks a fter the DEN injection, Control groups, were administered DEN alone. A ll rats were subjected to a partial (two-thirds) hepatectomy at the en d of week 3 and sacrificed at the end of week 8. The number and areas of GST-P (placental glutathione S-transferase)-positive foci induced i n the liver increased significantly as a result of treatment with 0.1% quinoline, and this increase was dramatic,vith 5-FQ at both doses, wh ereas no increases were noted with 3-FQ at either dose, Thus, the resu lts of the medium-term carcinogenicity assay predicted that quinoline, a hepatocarcinogen, would be deprived of carcinogenicity by fluorine atom substitution at position 3, and would conversely be endowed with a higher carcinogenic capacity by substitution at position 5, A semi-q uantitative relationship was demonstrated between carcinogenic and mut agenic potencies.