In vivo genotoxicity studies with p-benzoquinone dioxime.
P-Benzoquinone dioxime (BQD) appears to be a sex-specific rat carcinogen inducing tumours of the urinary bladder in female rats. The present paper shows that BQD is a direct-acting mutagen in Salmonella typhimurium TA98, confirming published data. In contrast to this in vitro data, negative results were obtained after oral administration of BQD to female rats in both the bone marrow micronucleus test and the in vivo liver UDS test. BQD did, however, induce a marked effect upon S-phase synthesis in the livers of female rats between 14 and 48 hr after a single oral dose of 250 mg/kg. A similar effect was also observed in the livers of male rats. There was no evidence of hepatotoxicity (in terms of elevated liver enzyme levels) after treatment of female rats with the compound indicating that the increase in cell proliferation was due to a direct mitogenic effect of BQD in this organ. Some liver mitogens have been found to be liver carcinogens; this does not appear to be the case for BQD. Nevertheless, the mitogenic activity of this compound might play a contributory role to the induction of bladder cancer in rats if it also acted as a mitogen in this tissue. Further studies are indicated, measuring genotoxicity and cell-proliferative activity in the bladder in order to further elucidate the mechanism of action of this compound as a rodent carcinogen.
Westmoreland
C
C
Genetic and Reproductive Toxicology Department, Glaxo Group Research Ltd., Ware, Herts, United Kingdom.
George
E
E
York
M
M
Gatehouse
D
D
D000284:Administration, Oral; D000818:Animals; D016227:Benzoquinones / Q000633:toxicity*; D001853:Bone Marrow / Q000187:drug effects; D015197:Carcinogenicity Tests; D002455:Cell Division / Q000187:drug effects; D005260:Female; D008099:Liver / Q000187:drug effects; D008297:Male; D015162:Micronucleus Tests; D008934:Mitogens / Q000633:toxicity; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D010091:Oximes / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects
D016227:Benzoquinones; D008934:Mitogens; D009153:Mutagens; D010091:Oximes; C035388:1,4-benzoquinone dioxime