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The metabolic activation of 7‐methylbenz(a)anthracene: The induction of malignant transformation and mutation in mammalian cells by non‐K‐region dihydrodiols
Author(s) -
Marquardt H.,
Baker S.,
Tierney B.,
Grover P. L.,
Sims P.
Publication year - 1977
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910190614
Subject(s) - anthracene , diol , carcinogen , chemistry , stereochemistry , epoxide , chinese hamster , 7,12 dimethylbenz[a]anthracene , vicinal , biochemistry , in vitro , organic chemistry , carcinogenesis , gene , catalysis , dmba
Four different dihydrodiols derived from 7‐methylbenz(a)anthracene have been tested, together with the parent hydrocarbon, for their ability to induce the in vitro malignant transformation of mouse M2 fibroblasts and mutations in V79 Chinese hamster cells. In the transformation tests with the non‐K‐region dihydrodiols, the 3,4‐diol was the most active dihydrodiol tested and the 8,9‐diol was also more active than 7‐methylbenz(a)anthracene itself; the 1,2‐diol showed only slight activity. The K‐region dihydrodiol, the 5,6‐diol, which cannot be directly metabolized to a vicinal diol‐epoxide, was inactive. These differences in biological activity were similar to those apparent in the results from the mutagenicity tests. The data support the general hypothesis that non‐K‐region dihydrodiols, which can be metabolized to vicinal diol‐epoxides, are important in the metabolic activation of the carcinogenic polycyclic hydrocarbons and, when taken together with other results, indicate that 3,4‐dihydro‐3,4‐dihydroxy‐7‐methylbenz(a)anthracene is most probably involved in the metabolic activation of 7‐methylbenz(a)anthracene presumably following conversion into the related diol‐epoxide, 3,4‐dihydro‐3,4‐dihydroxy‐7‐methylbenz(a)anthracene 1,2‐oxide.