The selective effect of genistein on the toxicity of bleomycin in normal lymphocytes and HL-60 cells.
This study was carried out to find whether genistein might enhance bleomycin induced cytotoxicity in human leukemia (HL-60) while protecting normal blood lymphocytes. Despite the excellent chemotherapeutic effect of bleomycin, its cytotoxicity and genotoxicity in normal cells remains a major problem in chemotherapy. Genistein, one of the major Soy isoflavones, is particularly effective in quenching free radicals generated by toxic agents. In this study, the protective and enhancement effects of genistein on bleomycin induced cytotoxicity in HL-60 cells and blood lymphocytes were demonstrated. HL-60 cells were treated with various concentrations of genistein for 3 h followed by treatment with various concentrations of bleomycin during the G1 phase. Pretreatment of genistein increased micronuclei (MN) frequency and DNA damage as a result of bleomycin treatment. However, when human lymphocytes were pretreated with genistein prior to bleomycin treatment during the G2 or G0 phase, the frequencies of bleomycin induced MN was decreased. Although the extent of bleomycin induced DNA damage determined by single cell gel electrophoresis was increased through the pretreatment of genistein in HL-60 cells, it was decreased in normal lymphocytes. The result of this study may therefore provide great impact on the potential activity of genistein as a therapeutic agent.
Lee
Rami
R
School of Public Health and Institute of Health and Environmental Sciences, Seoul National University, 28 Yunkeun-dong, Chongno-ku, Seoul 110-460, South Korea.
Kim
Yang Jee
YJ
Lee
Young Joon
YJ
Chung
Hai Won
HW
D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D001761:Bleomycin / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D018922:HL-60 Cells / Q000187:drug effects*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects*; D015162:Micronucleus Tests
D000903:Antibiotics, Antineoplastic; D004273:DNA, Neoplasm; D001761:Bleomycin; D019833:Genistein