COMPARISON OF MUTAGENESIS AND MALIGNANT TRANSFORMATION BY DIHYDRODIOLS FROM BENZ[A]ANTHRACENE AND 7,12-DIMETHYLBENZ[A]ANTHRACENE

被引:16
作者
MARQUARDT, H
BAKER, S
TIERNEY, B
GROVER, PL
SIMS, P
机构
[1] ROYAL CANC HOSP, CHESTER BEATTY RES INST, INST CANC RES, LONDON SW3 6JB, ENGLAND
[2] MEM SLOAN KETTERING CANC CTR, NEW YORK, NY 10021 USA
基金
美国国家卫生研究院; 英国医学研究理事会;
关键词
D O I
10.1038/bjc.1979.99
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Five dihydrodiols derived from benz[a]anthracene (BA) and 4 dihydrodiols derived from 7,12-dimethylbenz[a]anthracene (DMBA) have been tested, together with the parent hydrocarbons, for their abilities to induce mutations to 8-azaguanine resistance in V79 Chinese hamster cells and malignant transformation in M2 mouse fibroblasts. The syn- and antisomers of benz[a]anthracene 8,9-diol 10,11-oxide were also tested for biological activity in these two systems. The non-K-region 1,2- and 3,4-dihydrodiols of BA induced mutations but the non-K-region 8,9-dihydrodiol and the K-region 5,6-dihydrodiol were inactive as mutagens; none of these BA diols transformed M2 mouse fibroblasts. The 3,4- and the 8,9-dihydrodiols derived from 7,12-dimethylbenz[a]anthracene induced mutations in V79 cells and malignant transformation in M2 mouse fibroblasts and both were more active than the hydrocarbon itself. The K-region 5,6-dihydrodiol and the non-K-region 10,11-dihydrodiol of DMBA were inactive in both test systems. The results are not inconsistent with other data suggesting that the metabolic activation of both BA and DMBA occurs through conversion of the respective 3,4-dihydrodiols into the related vicinal diol-epoxides, although other dihydrodiols may also be involved in vivo. Both the BA diol-epoxides tested were mutagenic, but although the anti-isomer transformed M2 fibroblasts, the syn-isomer was inactive. © 1979, Nature Publishing Group. All Rights Reserved.
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页码:540 / 547
页数:8
相关论文
共 45 条
[1]  
BAIRD W M, 1973, Cancer Research, V33, P2378
[2]   8,9-DIHYDRO-8,9-DIHYDROXYBENZ(A)ANTHRACENE 10,11-OXIDE - NEW TYPE OF POLYCYCLIC AROMATIC HYDROCARBON METABOLITE [J].
BOOTH, J ;
SIMS, P .
FEBS LETTERS, 1974, 47 (01) :30-33
[3]   METABOLIC CONVERSION OF BENZO[ALPHA]PYRENE BY SYRIAN-HAMSTER LIVER-MICROSOMES AND BINDING OF METABOLITES TO DEOXYRIBONUCLEIC ACID [J].
BORGEN, A ;
DARVEY, H ;
CASTAGNO.N ;
CROCKER, TT ;
RASMUSSE.RE ;
WANG, IY .
JOURNAL OF MEDICINAL CHEMISTRY, 1973, 16 (05) :502-506
[4]   METABOLISM OF POLYCYCLIC COMPOUNDS .24. METABOLISM OF BENZ(A)ANTHRACENE [J].
BOYLAND, E ;
SIMS, P .
BIOCHEMICAL JOURNAL, 1964, 91 (03) :493-&
[5]   METABOLISM OF POLYCYCLIC COMPOUNDS - METABOLISM OF 7,12-DIMETHYLBENZ(A)ANTHRACENE BY RAT-LIVER HOMOGENATES [J].
BOYLAND, E ;
SIMS, P .
BIOCHEMICAL JOURNAL, 1965, 95 (03) :780-&
[6]   EFFECT OF PRETREATMENT WITH ADRENAL-PROTECTING COMPOUNDS ON METABOLISM OF 7,12-DIMETHYLBENZ[A]ANTHRACENE AND RELATED COMPOUNDS BY RAT-LIVER HOMOGENATES [J].
BOYLAND, E ;
SIMS, P .
BIOCHEMICAL JOURNAL, 1967, 104 (02) :394-+
[7]  
CHEN TT, 1969, JNCI-J NATL CANCER I, V42, P903
[8]   TUMOR-INITIATING ACTIVITIES ON MOUSE SKIN OF DIHYDRODIOLS DERIVED FROM BENZO[A]PYRENE [J].
CHOUROULINKOV, I ;
GENTIL, A ;
GROVER, PL ;
SIMS, P .
BRITISH JOURNAL OF CANCER, 1976, 34 (05) :523-532
[9]   METABOLIC ACTIVATION OF 7-METHYLBENZ(A)ANTHRACENE IN MOUSE SKIN - HIGH TUMOR-INITIATING ACTIVITY OF 3,4-DIHYDRODIOL [J].
CHOUROULINKOV, I ;
GENTIL, A ;
TIERNEY, B ;
GROVER, P ;
SIMS, P .
CANCER LETTERS, 1977, 3 (5-6) :247-253
[10]   MAMMALIAN CELL GENETICS .2. CHEMICAL INDUCTION OF SPECIFIC LOCUS MUTATIONS IN CHINESE HAMSTER CELLS IN VITRO [J].
CHU, EHY ;
MALLING, HV .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1968, 61 (04) :1306-&