Quinoline: unscheduled DNA synthesis and mitogenesis data from the rat liver in vivo.
Quinoline is a specific and potent carcinogen to the rat and mouse liver. Studies are described here in which it was evaluated for its ability to initiate unscheduled DNA synthesis (UDS) in the rat liver in vivo. Although some individual animals showed indications of a marginal response the absence of clear group positive responses and the lack of an obvious dose relationship precluded the classification of quinoline as positive. The analogous NTP non-carcinogen 8-hydroxyquinoline was shown also to be devoid of UDS activity. Quinoline did, however, induce a potent mitogenic response in the rat liver between 24 and 48 hr after oral dosing of 200-500 mg/kg. Under similar conditions of test, 8-hydroxyquinoline was essentially inactive. These data represent a further instance in which mitogenicity in the liver appears to correlate better with carcinogenicity than does genotoxicity; but it may not be that simple, as discussed in the text. A single dose of quinoline was shown to act as a replacement for surgical partial hepatectomy in the liver micronucleus assay described by Tates, consistent with its potent mitogenicity.
Ashby
J
J
ICI Central Toxicology Laboratory, Macclesfield Cheshire, UK.
Mohammed
R
R
Lefevre
P A
PA
Bandara
L
L
D000818:Animals; D004247:DNA / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D006912:Hydroxyquinolines / Q000633:toxicity*; D007399:Interphase / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D048629:Micronuclei, Chromosome-Defective; D015162:Micronucleus Tests; D008934:Mitogens; D008938:Mitosis / Q000187:drug effects*; D015125:Oxyquinoline / Q000633:toxicity*; D011804:Quinolines / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
D006912:Hydroxyquinolines; D008934:Mitogens; D011804:Quinolines; D015125:Oxyquinoline; D004247:DNA; C037219:quinoline