Effect of hepatic cytochrome P-450 inducing agents on mutagen activity in the host-mediated assay.
Intraperitoneal treatment of female BALB/c mice with either phenobarbitone or beta-naphthoflavone led to the induction of various hepatic enzymes associated with xenobiotic metabolism and to increased abilities of hepatic S9 fractions to convert the dietary carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) to an active bacterial mutagen. In the case of another carcinogen, aflatoxin B1 an increase in in vitro hepatic activation was seen only in mice treated with phenobarbitone. In contrast, pretreatment with either phenobarbitone or beta-naphthoflavone reduced the in vivo activity of both aflatoxin B1 and MeIQx in the host mediated bacterial mutation assay. These data indicate that, for some carcinogens at least, the host-mediated assay may be used to predict the carcinogenic consequences of hepatic enzyme induction.
Alldrick
A J
AJ
BIBRA Toxicology International, Carshalton, UK.
Brennan-Craddock
W E
WE
Lake
B G
BG
Rowland
I R
IR
D000348:Aflatoxins / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001571:Benzoflavones / Q000378:metabolism; D002273:Carcinogens / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004790:Enzyme Induction; D005260:Female; D008099:Liver / Q000201:enzymology; D051379:Mice; D008807:Mice, Inbred BALB C; D016296:Mutagenesis; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000378:metabolism*; D010634:Phenobarbital / Q000378:metabolism; D011810:Quinoxalines / Q000378:metabolism*; D012486:Salmonella typhimurium; D019324:beta-Naphthoflavone
D000348:Aflatoxins; D001571:Benzoflavones; D002273:Carcinogens; D009153:Mutagens; D011810:Quinoxalines; D019324:beta-Naphthoflavone; C036990:2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital