Evaluation of positive controls for the in vitro unscheduled DNA synthesis assay using hepatocytes from induced (Aroclor 1254) and uninduced male cynomolgus monkey.
We have evaluated the use of four different positive control compounds for assessing UDS in monkey hepatocytes and have found three of these, methylmethanesulfonate, benzo[a]pyrene, and dimethylbenz[a]anthracene, to produce strong positive responses in vitro. Dimethylnitrosamine induced only weak responses. We also report that the strength of the response induced by procarcinogens was not enhanced in hepatocytes taken from Aroclor 1254-pretreated monkeys, even though substantial induction of cytochrome P450 enzymes was demonstrated in these cells. These studies raise the question of the utility of employing an in vivo induction system to enhance the monkey UDS assay.
Hamilton
C M
CM
SRI International, Menlo Park, California 94025-3493, USA. carol_hamilton@qm.sri.com
Dabbs
J E
JE
Cunningham
G D
GD
Vernetti
L A
LA
Mirsalis
J C
JC
Snyder
R D
RD
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D001140:Aroclors / Q000494:pharmacology*; D001564:Benzo(a)pyrene / Q000633:toxicity; D001711:Biotransformation; D004260:DNA Repair; D004128:Dimethylnitrosamine / Q000633:toxicity; D004790:Enzyme Induction; D008099:Liver; D008252:Macaca fascicularis; D008297:Male; D008741:Methyl Methanesulfonate / Q000633:toxicity; D009152:Mutagenicity Tests / Q000379:methods*
D001140:Aroclors; D001564:Benzo(a)pyrene; D015127:9,10-Dimethyl-1,2-benzanthracene; D008741:Methyl Methanesulfonate; D004128:Dimethylnitrosamine