QUANTITATIVE COMPARISON OF THE MUTAGENICITY OF CARCINOGENIC POLYCYCLIC-HYDROCARBON DERIVATIVES IN CULTURED MAMMALIAN-CELLS

被引:53
作者
NEWBOLD, RF [1 ]
BROOKES, P [1 ]
HARVEY, RG [1 ]
机构
[1] UNIV CHICAGO, BEN MAY LAB CANC RES, CHICAGO, IL 60637 USA
关键词
D O I
10.1002/ijc.2910240212
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The mutagenicity of a series of reactive polycyclic hydrocarbon derivatives has been studied using Chinese hamster (V79) cells in culture and, as a mutational marker, resistance to the purine analogue 8‐azaguanine. The compounds were compared by relating mutation frequency to the dose applied (mutagenic effectiveness) to induced cytotoxicity (mutagenic efficiency) and to the extent of reaction of the hydrocarbon with DNA (absolute mutagenic efficiency). In each case anti‐benzo(a)pyrene (BP)—7,8 dihydrodiol‐9,10 oxide, the suspected ultimate carcinogenic form of benzo(a)pyrene, was by far the most potent of the compounds tested. Furthermore, the mutagenicity of the syn‐ and anti‐BP‐diolepoxide isomers correlated positively with their documented carcinogenic potency. Differences in mutagenic effectiveness are ascribed to predicted differences in the ability of each derivative to form a carbonium ion. Variations in mutagenic efficiency and absolute mutagenic efficiency were more difficult to explain. The latter findings are discussed in relation to the types of hydrocarbon‐DNA product obtained with each compound and also to the possibility of a variable cellular response to more subtle differences in the chemistry of the hydrocarbon‐DNA interaction. Copyright © 1979 Wiley‐Liss, Inc., A Wiley Company
引用
收藏
页码:203 / 209
页数:7
相关论文
共 42 条
[1]   EVIDENCE FOR BINDING OF POLYNUCLEAR AROMATIC HYDRO-CARBONS TO NUCLEIC ACIDS OF MOUSE SKIN - RELATION BETWEEN CARCINOGENIC POWER OF HYDROCARBONS + THEIR BINDING TO DEOXYRIBONUCLEIC ACID [J].
BROOKES, P ;
LAWLEY, PD .
NATURE, 1964, 202 (493) :781-&
[2]   BINDING TO MOUSE SKIN DNA OF BENZO[A]PYRENE, ITS 7,8-DIOL AND 7,8-DIOL-9,10-EPOXIDES IN RELATION TO THE TUMORIGENICITY OF THESE COMPOUNDS [J].
BROOKES, P .
CANCER LETTERS, 1979, 6 (4-5) :285-289
[3]  
BROOKES P, 1976, MUTAT RES, V38, P155
[4]   TUMORIGENICITY OF OPTICAL ENANTIOMERS OF DIASTEREOMERIC BENZO[A]PYRENE 7,8-DIOL-9,10-EPOXIDES IN NEWBORN MICE - EXCEPTIONAL ACTIVITY OF(+)-7-BETA, 8-ALPHA-DIHYDROXY-9-ALPHA, 10-ALPHA-EPOXY-7,8.9.10-TETRAHYDROBENZOL[A]PYRENE [J].
BUENING, MK ;
WISLOCKI, PG ;
LEVIN, W ;
YAGI, H ;
THAKKER, DR ;
AKAGI, H ;
KOREEDA, M ;
JERINA, DM ;
CONNEY, AH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1978, 75 (11) :5358-5361
[5]   THE RATES OF SOLVOLYSIS OF CERTAIN ARYLMETHYL CHLORIDES, AND A SIMPLE MOLECULAR-ORBITAL TREATMENT OF THIS AND SIMILAR REACTIONS [J].
DEWAR, MJS ;
SAMPSON, RJ .
JOURNAL OF THE CHEMICAL SOCIETY, 1956, (AUG) :2789-2797
[6]   THE SOLVOLYSIS OF ARYLMETHYL CHLORIDES .3. FURTHER DEMONSTRATION OF RETARDATION OF SOLVOLYSIS RATES OF PERI-COMPOUNDS [J].
DEWAR, MJS ;
SAMPSON, RJ .
JOURNAL OF THE CHEMICAL SOCIETY, 1957, (JUL) :2952-2954
[7]   THE SOLVOLYSIS OF ARYLMETHYL CHLORIDES .2. A MOLECULAR-ORBITAL TREATMENT AND FURTHER EXPERIMENTAL EVIDENCE OF THE TRANSITION FROM THE LIMITING TO THE FULLY NUCLEOPHIL-ASSISTED MECHANISM [J].
DEWAR, MJS ;
SAMPSON, RJ .
JOURNAL OF THE CHEMICAL SOCIETY, 1957, (JUL) :2946-2952
[8]  
DIAMOND L, 1967, CANCER RES, V27, P890
[9]   REACTION OF 7-BROMOMETHYLBENZ[A]ANTHRACENE WITH NUCLEIC ACIDS, POLYNUCLEOTIDES, AND NUCLEOSIDES [J].
DIPPLE, A ;
BROOKES, P ;
MACKINTOSH, DS ;
RAYMAN, MP .
BIOCHEMISTRY, 1971, 10 (23) :4323-+
[10]  
DIPPLE A, 1968, EUR J CANCER, V4, P439