title: Sulforaphane inhibits CYP1A1 activity and promotes genotoxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in vitro.
abstract: Increasing environmental pollution by carcinogens such as some of persistent organic pollutants (POPs) has prompted growing interest in searching for chemopreventive compounds which are readily obtainable. Sulforaphane (SFN) is isolated from cruciferous vegetables and has the potentials to reduce carcinogenesis through various pathways. In this study, we studied the effects of SFN on CYP1A1 activity and genotoxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The results showed that SFN inhibited TCDD-induced CYP1A1 activity in H4IIE cells by directly inhibiting CYP1A1 activity, probably through binding to aryl hydrocarbon receptor and/or CYP1A1 revealed by molecular docking. However, SFN promoted TCDD-induced DNA damage in yeast cells and reduced the viability of initiated yeast cells. Besides, it is surprising that SFN also failed to reduce genotoxicity induced by other genotoxic reagents which possess different mechanisms to lead to DNA damage. Currently, it is difficult to predict whether SFN has the potentials to reduce the risk of TCDD based on the conflicting observations in the study. Therefore, further studies should be urgent to reveal the function and mechanism of SFN in the stress of such POPs on human health.
authors.affiliation: MOE Key Laboratory of Environmental Remediation and Ecosystem Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou, 310058, China. fxyang@zju.edu.cn
authors.forename: Fangxing
authors.initials: F
authors.lastname: Yang
authors.forename: Shulin
authors.initials: S
authors.lastname: Zhuang
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.forename: Heping
authors.initials: H
authors.lastname: Dai
authors.forename: Weiping
authors.initials: W
authors.lastname: Liu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors*; D004249:DNA Damage / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D017879:Isothiocyanates; D009152:Mutagenicity Tests; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D051381:Rats; D012441:Saccharomyces cerevisiae / Q000187:drug effects; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology / Q000633:toxicity*
chemical_list: D017879:Isothiocyanates; D000072317:Polychlorinated Dibenzodioxins; D013454:Sulfoxides; D013861:Thiocyanates; D019363:Cytochrome P-450 CYP1A1; C016766:sulforaphane