Effect of some cooked food mutagens on unscheduled DNA synthesis in cultured precision-cut rat, mouse and human liver slices.
Precision-cut liver slices were prepared from male Fischer 344 rats, female CDF1 mice and humans (both male and female subjects). Liver slices were cultured for 24 hr in medium containing [3H]thymidine and either PhIP, IQ, MeIQ, MeIQx, Glu-P-1 or Trp-P-1, and then processed for auto-radiographic evaluation of unscheduled DNA synthesis (UDS). All six cooked food mutagens examined produced concentration-dependent increases in UDS in human liver slices. PhIP was the most potent compound examined, followed by MeIQx, IQ and then MeIQ, Glu-P-1 and Trp-P-1. Significant increases in UDS were observed with PhIP, IQ and MeIQx at concentrations as low as 5 microM in the culture medium. The same rank order of potency was not apparent in either rat or mouse liver slices. In rat liver slices only MeIQ significantly induced UDS, although positive results were obtained with two other genotoxins, namely 2-acetylaminofluorene and aflatoxin B1. Apart from MeIQx, all the cooked food mutagens produced significant increases in UDS in mouse liver slices. This study demonstrates the usefulness of precision-cut liver slices to evaluate species differences in xenobiotic-induced genotoxicity. Both marked compound and species differences in induction of UDS were observed. The data provide further evidence that dietary cooked food mutagens are potential human carcinogens.
BIBRA International, Carshalton, Surrey, UK.
J A
JA
Beamand
P T
PT
Barton
J M
JM
Tredger
R J
RJ
Price
B G
BG
Lake
D015073:2-Acetylaminofluorene / Q000633:toxicity; D016604:Aflatoxin B1 / Q000633:toxicity; D000818:Animals; D001345:Autoradiography; D002243:Carbolines / Q000633:toxicity; D003296:Cooking; D046508:Culture Techniques; D004247:DNA / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000633:toxicity; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D009153:Mutagens / Q000633:toxicity*; D011804:Quinolines / Q000633:toxicity; D011810:Quinoxalines / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D013329:Structure-Activity Relationship
D002243:Carbolines; D007093:Imidazoles; D009153:Mutagens; D011804:Quinolines; D011810:Quinoxalines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; C023785:2-amino-6-methyldipyrido(1,2-a-3',2'-d)imidazole; C036990:2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline; D004247:DNA; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D015073:2-Acetylaminofluorene; D016604:Aflatoxin B1; C019132:3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole