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Endogenous estrogen status, but not genistein supplementation, modulates 7,12‐dimethylbenz[ a ]anthracene‐induced mutation in the liver cII gene of transgenic big blue rats
Author(s) -
Chen Tao,
Hutts Robert C.,
Mei Nan,
Liu Xiaoli,
Bishop Michelle E.,
Shelton Sharon,
Manjanatha Mugimane G.,
Aidoo Anane
Publication year - 2005
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.20102
Subject(s) - 7,12 dimethylbenz[a]anthracene , genistein , estrogen , endogeny , transgene , mutation , gene , biology , gene mutation , mutagen , genetically modified mouse , genetics , microbiology and biotechnology , carcinogen , cancer research , endocrinology , chemistry , dmba , carcinogenesis
A growing number of studies suggest that isoflavones found in soybeans have estrogenic activity and may safely alleviate the symptoms of menopause. One of these isoflavones, genistein, is commonly used by postmenopausal women as an alternative to hormone replacement therapy. Although sex hormones have been implicated as an important risk factor for the development of hepatocellular carcinoma, there are limited data on the potential effects of the estrogens, including phytoestrogens, on chemical mutagenesis in liver. Because of the association between mutation induction and the carcinogenesis process, we investigated whether endogenous estrogen and supplemental genistein affect 7,12‐dimethylbenz[ a ]anthracene (DMBA)‐induced mutagenesis in rat liver. Intact and ovariectomized female Big Blue rats were treated with 80 mg DMBA/kg body weight. Some of the rats also received a supplement of 1,000 ppm genistein. Sixteen weeks after the carcinogen treatment, the rats were sacrificed, their livers were removed, and mutant frequencies (MFs) and types of mutations were determined in the liver cII gene. DMBA significantly increased the MFs in liver for both the intact and ovariectomized rats. While there was no significant difference in MF between the ovariectomized and intact control animals, the mutation induction by DMBA in the ovariectomized groups was significantly higher than that in the intact groups. Dietary genistein did not alter these responses. Molecular analysis of the mutants showed that DMBA induced chemical‐specific types of mutations in the liver cII gene. These results suggest that endogenous ovarian hormones have an inhibitory effect on liver mutagenesis by DMBA, whereas dietary genistein does not modulate spontaneous or DMBA‐induced mutagenesis in either intact or ovariectomized rats. Environ. Mol. Mutagen., 2005. Published 2005 Wiley‐Liss, Inc.