-transparent.png){kind=logo}
The 12 isomeric phenols of benzo(a)pyrene were tested for their ability to inhibit the mutagenic activity of (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene [B(a)P 7,8-diol-9,10-epoxide-2], an ultimate mutagenic and carcinogenic metabolite of benzo(a)pyrene. 3-Hydroxybenzo(a)pyrene [3-HO-B(a)P], a major metabolite of benzo(a)pyrene, was the most potent antagonist tested. Approximately 3 nmol of 3-HO-B(a)P, 14 nmol of 10-HO-B(a)P, and 5-8 nmol of 1-, 2-, 4-, 5-, 6-, 7-, 8-, 9-, 11-, and 12-HO-B(a)P inhibited the mutagenic activity of 0.05 nmol of B(a)P 7,8-diol-9,10-epoxide-2 by 50% in Salmonella typhimurium strain TA 100. The importance of the phenolic group for antimutagenic activity was indicated by the lack of antimutagenic activity of benzo(a)pyrene itself. 3-HO-B(a)P also inhibited the mutagenic activity resulting from the metabolic activation of benzo(a)pyrene and (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene by rat liver microsomes. This inhibition may have resulted from an effect of 3-HO-B(a)P on the metabolic activation of these carcinogens and/or from a direct effect on the action of B(a)P 7,8-diol-9,10-epoxide-2. In a mammalian cell culture system utilizing Chinese hamster V79 cells, 3-HO-B(a)P (8 microM) inhibited the mutagenicity of B(a)P 7,8-diol-9,10-epoxide-2 (0.2 microM) by 50%. Although 3-HO-B(a)P was a potent inhibitor of the mutagenic activity of bay-region diol epoxides of benzo(a)pyrene, dibenzo(a,h)pyrene, and dibenzo(a,i)pyrene in S. typhimurium strain TA 100, higher concentrations of 3-HO-B(a)P were needed to inhibit the mutagenicity of the chemically less reactive benzo(a)pyrene 4,5-oxide and the bay-region diol epoxides of benz(a)anthracene, chrysene, and benzo(c)phenanthrene. Both 3-HO-B(a)P and 10-HO-B(a)P accelerated the disappearance of B(a)P 7,8-diol-9,10-epoxide-2 from 1:9 dioxane-water solutions at pH 7 and 25 degrees C. 3-HO-B(a)P, the most effective antimutagen of the B(a)P phenols tested, was much more reactive with the diol epoxide than 10-HO-B(a)P, the least effective antimutagen. The rate constant for the reaction of 3-HO-B(a)P with the diol epoxide exhibited a nonlinear (greater than first-order) dependence on the concentration of the phenol. Evidence was obtained for covalent adduct formation between the diol epoxide and each of the two phenols.(ABSTRACT TRUNCATED AT 400 WORDS)
M T Huang, and
A W Wood, and
R L Chang, and
H Yagi, and
J M Sayer, and
D M Jerina, and
A H Conney
December 1979,
FEBS letters,
M T Huang, and
A W Wood, and
R L Chang, and
H Yagi, and
J M Sayer, and
D M Jerina, and
A H Conney
September 1984,
Molecular pharmacology,
M T Huang, and
A W Wood, and
R L Chang, and
H Yagi, and
J M Sayer, and
D M Jerina, and
A H Conney
January 1989,
Chemico-biological interactions,
M T Huang, and
A W Wood, and
R L Chang, and
H Yagi, and
J M Sayer, and
D M Jerina, and
A H Conney
March 1992,
Proceedings of the National Academy of Sciences of the United States of America,
M T Huang, and
A W Wood, and
R L Chang, and
H Yagi, and
J M Sayer, and
D M Jerina, and
A H Conney
January 1987,
Chemico-biological interactions,
M T Huang, and
A W Wood, and
R L Chang, and
H Yagi, and
J M Sayer, and
D M Jerina, and
A H Conney
April 1983,
Cancer research,
M T Huang, and
A W Wood, and
R L Chang, and
H Yagi, and
J M Sayer, and
D M Jerina, and
A H Conney
January 1988,
Cancer letters,
M T Huang, and
A W Wood, and
R L Chang, and
H Yagi, and
J M Sayer, and
D M Jerina, and
A H Conney
January 1983,
Carcinogenesis,
M T Huang, and
A W Wood, and
R L Chang, and
H Yagi, and
J M Sayer, and
D M Jerina, and
A H Conney
January 1982,
Carcinogenesis,
M T Huang, and
A W Wood, and
R L Chang, and
H Yagi, and
J M Sayer, and
D M Jerina, and
A H Conney
January 1986,
Carcinogenesis,
