ENZYMATIC PHASE-II ACTIVATION OF THE N-HYDROXYLAMINES OF IQ, MEIQX AND PHIP BY VARIOUS ORGANS OF MONKEYS AND RATS

被引:85
作者
DAVIS, CD [1 ]
SCHUT, HAJ [1 ]
SNYDERWINE, EG [1 ]
机构
[1] MED COLL OHIO,DEPT PATHOL,TOLEDO,OH 43614
关键词
D O I
10.1093/carcin/14.10.2091
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
2-Amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are mutagenic and carcinogenic heterocyclic amines produced during the ordinary cooking of meat. These compounds undergo metabolic activation via both cytochrome P450-mediated N-oxidation and phase II esterification in order to exert their genotoxicity. In the current study, we examined the in vitro phase II activation of N-hydroxy-IQ, N-hydroxy-PhIP and N-hydroxy-MeIQx by cytosolic acetyltransferase, sulfotransferase, aminoacyl-tRNA synthetase and phosphatase from a number of tissues including liver, kidney, colon and heart. These tissues were chosen for study because each is either a target organ for carcinogenicity or has displayed high levels of DNA adducts in in vivo studies with the heterocyclic amines. Cytosol from various tissues of both monkeys and rats was incubated with and without the respective cofactors, and carcinogen binding to calf thymus DNA was measured by P-32-postlabeling analysis. Our results show that all four phase II enzymes may participate in the activation of the N-hydroxylamines. However, the degree of activation depends on the substrate, tissue and animal species. For example, in both monkeys and rats, the highest acetyl CoA-enhanced binding was observed with N-hydroxy-IQ and the lowest acetyl CoA-enhanced binding was observed with N-hydroxy-MeIQx. In contrast, no significant adenosine 3'-phosphate 5'-phosphosulfate-dependent activation of N-hydroxy-IQ was observed with monkey cytosol from liver, kidney, heart or colon but the sulfotransferase-mediated activation of N-hydroxy-PhIP was at least 10 times higher in all four tissues of monkeys than in rats. Prolylation appears important in the activation of all three N-hydroxylamines by rat liver and heart cytosol, whereas in monkeys, prolylation appears important in kidney cytosol. The differences observed in the phase II activation of heterocyclic amines may have implications for DNA adduct formation, toxicity and carcinogenicity.
引用
收藏
页码:2091 / 2096
页数:6
相关论文
共 40 条
[1]   SULFOTRANSFERASE-MEDIATED DNA-BINDING OF N-HYDROXYARYLAMINES(AMIDE) IN LIVER CYTOSOLS FROM HUMAN AND EXPERIMENTAL-ANIMALS [J].
ABUZEID, M ;
YAMAZOE, Y ;
KATO, R .
CARCINOGENESIS, 1992, 13 (08) :1307-1314
[2]  
ADAMSON RH, 1991, XENOBIOTICS AND CANCER, P289
[3]  
ADAMSON RH, 1990, JPN J CANCER RES, V78, P297
[4]   ROLE OF SULFATION AND ACETYLATION IN THE ACTIVATION OF 2-HYDROXYAMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE TO INTERMEDIATES WHICH BIND DNA [J].
BUONARATI, MH ;
TURTELTAUB, KW ;
SHEN, NH ;
FELTON, JS .
MUTATION RESEARCH, 1990, 245 (03) :185-190
[5]  
DAVIS CD, 1993, FASEB J, V7, pA136
[6]   MUTAGENIC ACTIVATION OF IQ, PHIP AND MEIQX BY HEPATIC MICROSOMES FROM RAT, MONKEY AND MAN - LOW MUTAGENIC ACTIVATION OF MEIQX IN CYNOMOLGUS MONKEYS INVITRO REFLECTS LOW DNA ADDUCT LEVELS INVIVO [J].
DAVIS, CD ;
SCHUT, HAJ ;
ADAMSON, RH ;
THORGEIRSSON, UP ;
THORGEIRSSON, SS ;
SNYDERWINE, EG .
CARCINOGENESIS, 1993, 14 (01) :61-65
[7]  
DAVIS CD, 1993, IN PRESS CANCER LETT
[8]   INDUCTION OF LYMPHOMA IN CDF1 MICE BY THE FOOD MUTAGEN, 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE [J].
ESUMI, H ;
OHGAKI, H ;
KOHZEN, E ;
TAKAYAMA, S ;
SUGIMURA, T .
JAPANESE JOURNAL OF CANCER RESEARCH, 1989, 80 (12) :1176-1178
[9]   OCCURRENCE, IDENTIFICATION, AND BACTERIAL MUTAGENICITY OF HETEROCYCLIC AMINES IN COOKED FOOD [J].
FELTON, JS ;
KNIZE, MG .
MUTATION RESEARCH, 1991, 259 (3-4) :205-217
[10]  
FLAMMANG TJ, 1985, MICROSOMES DRUG OXID, P190