Genetic damage and the inhibition of 7,12-dimethylbenz[a]anthracene-induced genetic damage by the phytoestrogens, genistein and daidzein, in female ICR mice

Ashok Kumar Giri, Leejane Lu

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42 Citations (Scopus)

Abstract

Populations consuming soybeans have reduced rates of breast, colon and prostate cancer possibly due, in part, to the presence in soybeans of two estrogenic isoflavones, genistein and daidzein. This study investigated the genotoxicity of these soya isoflavones and their interactions with 7,12-dimethylbenz[a]anthracene (DMBA)-induced sister chromatid exchanges (SCE) in bone marrow cells and DNA adduct formations in liver and mammary glands of mice. Groups of female ICR mice were pretreated i.p. with daidzein and/or genistein (10-20 mg/kg per day for 6 days or 50 mg/kg per 12 h for 3 days) or with the solvent, dimethylsulfoxide (DMSO). The mice were implanted with bromodeoxyuridine (BrdU) tablets s.c., and treated with DMBA (50 mg/kg) i.p. and colchicine (4 mg/kg) i.p. 24, 23, and 2 h before sacrifice, respectively. In bone marrow cells, DMBA alone induced 11.73 ± 1.42 SCE/cell compared to 4.35 ± 0.83 SCE/cell in the DMSO treated controls (P = 0.001). DMBA induced 20% fewer SCE (P < 0.05) in mice pretreated with daidzein, genistein or a combination of genistein and daidzein (6 × 20 mg/kg per day for 6 days) when compared to mice that received no pretreatments. Genistein at 50 mg/kg per 12 h for 3 days also inhibited DMBA-induced SCE by 20%. However, treatment for 3 days with 50 mg/kg per 12 h of genistein or daidzein alone, or a combination of daidzein plus genistein (without DMBA treatment) also induced more SCE than treatment with only the solvent (DMSO, P < 0.05). Pretreatment with both the low and the high doses of daidzein plus genistein or the high dose of genistein reduced the replication index of bone marrow cells when compared to pretreatment with DMSO (P < 0.05). Pretreatment with genistein reduced DMBA-induced DNA adduct formation by 34%, but this was only marginally significant (P = 0.08) due to the large inter-individual variability in adduct levels. These results show that genistein and daidzein suppress SCE and possibly DNA adduct formation induced by the known carcinogen, DMBA. This response to a low dose isoflavone exposure may be partly responsible for the protective effect against endocrine cancers of soya consumption.

Original languageEnglish (US)
Pages (from-to)125-133
Number of pages9
JournalCancer Letters
Volume95
Issue number1-2
DOIs
StatePublished - Aug 16 1995

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Phytoestrogens
Inbred ICR Mouse
Genistein
9,10-Dimethyl-1,2-benzanthracene
Sister Chromatid Exchange
Dimethyl Sulfoxide
Isoflavones
Bone Marrow Cells
DNA Adducts
Soybeans
anthracene
daidzein
Endocrine Gland Neoplasms
Colchicine
Bromodeoxyuridine
Human Mammary Glands
Carcinogens
Colonic Neoplasms
Tablets
Prostatic Neoplasms

Keywords

  • Breast cancer
  • Cell replication
  • Daidzein
  • DNA adducts
  • DNA damage
  • Genistein
  • Phytoestrogens
  • Prevention

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Molecular Biology

Cite this

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title = "Genetic damage and the inhibition of 7,12-dimethylbenz[a]anthracene-induced genetic damage by the phytoestrogens, genistein and daidzein, in female ICR mice",
abstract = "Populations consuming soybeans have reduced rates of breast, colon and prostate cancer possibly due, in part, to the presence in soybeans of two estrogenic isoflavones, genistein and daidzein. This study investigated the genotoxicity of these soya isoflavones and their interactions with 7,12-dimethylbenz[a]anthracene (DMBA)-induced sister chromatid exchanges (SCE) in bone marrow cells and DNA adduct formations in liver and mammary glands of mice. Groups of female ICR mice were pretreated i.p. with daidzein and/or genistein (10-20 mg/kg per day for 6 days or 50 mg/kg per 12 h for 3 days) or with the solvent, dimethylsulfoxide (DMSO). The mice were implanted with bromodeoxyuridine (BrdU) tablets s.c., and treated with DMBA (50 mg/kg) i.p. and colchicine (4 mg/kg) i.p. 24, 23, and 2 h before sacrifice, respectively. In bone marrow cells, DMBA alone induced 11.73 ± 1.42 SCE/cell compared to 4.35 ± 0.83 SCE/cell in the DMSO treated controls (P = 0.001). DMBA induced 20{\%} fewer SCE (P < 0.05) in mice pretreated with daidzein, genistein or a combination of genistein and daidzein (6 × 20 mg/kg per day for 6 days) when compared to mice that received no pretreatments. Genistein at 50 mg/kg per 12 h for 3 days also inhibited DMBA-induced SCE by 20{\%}. However, treatment for 3 days with 50 mg/kg per 12 h of genistein or daidzein alone, or a combination of daidzein plus genistein (without DMBA treatment) also induced more SCE than treatment with only the solvent (DMSO, P < 0.05). Pretreatment with both the low and the high doses of daidzein plus genistein or the high dose of genistein reduced the replication index of bone marrow cells when compared to pretreatment with DMSO (P < 0.05). Pretreatment with genistein reduced DMBA-induced DNA adduct formation by 34{\%}, but this was only marginally significant (P = 0.08) due to the large inter-individual variability in adduct levels. These results show that genistein and daidzein suppress SCE and possibly DNA adduct formation induced by the known carcinogen, DMBA. This response to a low dose isoflavone exposure may be partly responsible for the protective effect against endocrine cancers of soya consumption.",
keywords = "Breast cancer, Cell replication, Daidzein, DNA adducts, DNA damage, Genistein, Phytoestrogens, Prevention",
author = "Giri, {Ashok Kumar} and Leejane Lu",
year = "1995",
month = "8",
day = "16",
doi = "10.1016/0304-3835(95)03877-Y",
language = "English (US)",
volume = "95",
pages = "125--133",
journal = "Cancer Letters",
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T1 - Genetic damage and the inhibition of 7,12-dimethylbenz[a]anthracene-induced genetic damage by the phytoestrogens, genistein and daidzein, in female ICR mice

AU - Giri, Ashok Kumar

AU - Lu, Leejane

PY - 1995/8/16

Y1 - 1995/8/16

N2 - Populations consuming soybeans have reduced rates of breast, colon and prostate cancer possibly due, in part, to the presence in soybeans of two estrogenic isoflavones, genistein and daidzein. This study investigated the genotoxicity of these soya isoflavones and their interactions with 7,12-dimethylbenz[a]anthracene (DMBA)-induced sister chromatid exchanges (SCE) in bone marrow cells and DNA adduct formations in liver and mammary glands of mice. Groups of female ICR mice were pretreated i.p. with daidzein and/or genistein (10-20 mg/kg per day for 6 days or 50 mg/kg per 12 h for 3 days) or with the solvent, dimethylsulfoxide (DMSO). The mice were implanted with bromodeoxyuridine (BrdU) tablets s.c., and treated with DMBA (50 mg/kg) i.p. and colchicine (4 mg/kg) i.p. 24, 23, and 2 h before sacrifice, respectively. In bone marrow cells, DMBA alone induced 11.73 ± 1.42 SCE/cell compared to 4.35 ± 0.83 SCE/cell in the DMSO treated controls (P = 0.001). DMBA induced 20% fewer SCE (P < 0.05) in mice pretreated with daidzein, genistein or a combination of genistein and daidzein (6 × 20 mg/kg per day for 6 days) when compared to mice that received no pretreatments. Genistein at 50 mg/kg per 12 h for 3 days also inhibited DMBA-induced SCE by 20%. However, treatment for 3 days with 50 mg/kg per 12 h of genistein or daidzein alone, or a combination of daidzein plus genistein (without DMBA treatment) also induced more SCE than treatment with only the solvent (DMSO, P < 0.05). Pretreatment with both the low and the high doses of daidzein plus genistein or the high dose of genistein reduced the replication index of bone marrow cells when compared to pretreatment with DMSO (P < 0.05). Pretreatment with genistein reduced DMBA-induced DNA adduct formation by 34%, but this was only marginally significant (P = 0.08) due to the large inter-individual variability in adduct levels. These results show that genistein and daidzein suppress SCE and possibly DNA adduct formation induced by the known carcinogen, DMBA. This response to a low dose isoflavone exposure may be partly responsible for the protective effect against endocrine cancers of soya consumption.

AB - Populations consuming soybeans have reduced rates of breast, colon and prostate cancer possibly due, in part, to the presence in soybeans of two estrogenic isoflavones, genistein and daidzein. This study investigated the genotoxicity of these soya isoflavones and their interactions with 7,12-dimethylbenz[a]anthracene (DMBA)-induced sister chromatid exchanges (SCE) in bone marrow cells and DNA adduct formations in liver and mammary glands of mice. Groups of female ICR mice were pretreated i.p. with daidzein and/or genistein (10-20 mg/kg per day for 6 days or 50 mg/kg per 12 h for 3 days) or with the solvent, dimethylsulfoxide (DMSO). The mice were implanted with bromodeoxyuridine (BrdU) tablets s.c., and treated with DMBA (50 mg/kg) i.p. and colchicine (4 mg/kg) i.p. 24, 23, and 2 h before sacrifice, respectively. In bone marrow cells, DMBA alone induced 11.73 ± 1.42 SCE/cell compared to 4.35 ± 0.83 SCE/cell in the DMSO treated controls (P = 0.001). DMBA induced 20% fewer SCE (P < 0.05) in mice pretreated with daidzein, genistein or a combination of genistein and daidzein (6 × 20 mg/kg per day for 6 days) when compared to mice that received no pretreatments. Genistein at 50 mg/kg per 12 h for 3 days also inhibited DMBA-induced SCE by 20%. However, treatment for 3 days with 50 mg/kg per 12 h of genistein or daidzein alone, or a combination of daidzein plus genistein (without DMBA treatment) also induced more SCE than treatment with only the solvent (DMSO, P < 0.05). Pretreatment with both the low and the high doses of daidzein plus genistein or the high dose of genistein reduced the replication index of bone marrow cells when compared to pretreatment with DMSO (P < 0.05). Pretreatment with genistein reduced DMBA-induced DNA adduct formation by 34%, but this was only marginally significant (P = 0.08) due to the large inter-individual variability in adduct levels. These results show that genistein and daidzein suppress SCE and possibly DNA adduct formation induced by the known carcinogen, DMBA. This response to a low dose isoflavone exposure may be partly responsible for the protective effect against endocrine cancers of soya consumption.

KW - Breast cancer

KW - Cell replication

KW - Daidzein

KW - DNA adducts

KW - DNA damage

KW - Genistein

KW - Phytoestrogens

KW - Prevention

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