32P-postlabelling in studies of arylamine and nitroaromatic hydrocarbon activation and mutagenesis.
Carcinogenic arylamines and nitroaromatic hydrocarbons are chemicals that present occupational health hazards and share pathways of metabolic activation. The 32P-postlabelled DNA adducts formed in Chinese hamster ovary (CHO) cells treated with metabolites from two pathways that are common to the activation of the nitroaromatic hydrocarbon 6-nitrochrysene (6-NC) and the arylamine 6-aminochrysene (6-AC) compared with the spectra of mutations induced at the CHO hprt locus by these were metabolites. 6-Nitrosochrysene (6-NOC), which is reduced by the cells to N-hydroxy-6-AC, formed adducts mainly with deoxyguanosine, but induced mutations primarily through base-pair substitution involving deoxyadenosine. In contrast, 6-AC 1,2-dihydrodiol produced DNA adducts and mutations that mainly involved deoxyguanosine residues. The two major activation pathways for 6-NC and 6-AC thus produce distinct adduct and mutation spectra in CHO cells, and these adduct and mutational spectra are different from those of other arylamines and nitroaromatic hydrocarbons that have been studied.
Delclos
K B
KB
US Food and Drug Administration, National Center for Toxicological Research, Jefferson, AR 72079.
Manjanatha
M G
MG
Li
E E
EE
Newton
R K
RK
Mittelstaedt
R A
RA
Heflich
R H
RH
D000818:Animals; D001345:Autoradiography; D001711:Biotransformation; D016466:CHO Cells / Q000187:drug effects / Q000378:metabolism; D002911:Chrysenes / Q000493:pharmacokinetics* / Q000633:toxicity; D006224:Cricetinae; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D009153:Mutagens / Q000493:pharmacokinetics* / Q000633:toxicity; D010761:Phosphorus Radioisotopes
D002911:Chrysenes; D009153:Mutagens; D010761:Phosphorus Radioisotopes; C035986:6-nitrochrysene; D004247:DNA; D007041:Hypoxanthine Phosphoribosyltransferase; C100101:6-chrysenamine