PMID- 23566952 OWN - NLM STAT- MEDLINE DCOM- 20130717 LR - 20211203 IS - 1096-0333 (Electronic) IS - 0041-008X (Linking) VI - 269 IP - 3 DP - 2013 Jun 15 TI - Sulforaphane inhibits CYP1A1 activity and promotes genotoxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in vitro. PG - 226-32 LID - S0041-008X(13)00131-2 [pii] LID - 10.1016/j.taap.2013.03.024 [doi] AB - 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. CI - Copyright (c) 2013 Elsevier Inc. All rights reserved. FAU - Yang, Fangxing AU - Yang F AD - MOE Key Laboratory of Environmental Remediation and Ecosystem Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou, 310058, China. fxyang@zju.edu.cn FAU - Zhuang, Shulin AU - Zhuang S FAU - Zhang, Chao AU - Zhang C FAU - Dai, Heping AU - Dai H FAU - Liu, Weiping AU - Liu W LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130406 PL - United States TA - Toxicol Appl Pharmacol JT - Toxicology and applied pharmacology JID - 0416575 RN - 0 (Isothiocyanates) RN - 0 (Polychlorinated Dibenzodioxins) RN - 0 (Sulfoxides) RN - 0 (Thiocyanates) RN - EC 1.14.14.1 (Cytochrome P-450 CYP1A1) RN - GA49J4310U (sulforaphane) SB - IM MH - Animals MH - Cell Line, Tumor MH - Cytochrome P-450 CYP1A1/*antagonists & inhibitors MH - DNA Damage/drug effects MH - Dose-Response Relationship, Drug MH - Drug Synergism MH - Isothiocyanates MH - Mutagenicity Tests MH - Polychlorinated Dibenzodioxins/*toxicity MH - Rats MH - Saccharomyces cerevisiae/drug effects MH - Sulfoxides MH - Thiocyanates/pharmacology/*toxicity EDAT- 2013/04/10 06:00 MHDA- 2013/07/19 06:00 CRDT- 2013/04/10 06:00 PHST- 2012/11/02 00:00 [received] PHST- 2013/03/11 00:00 [revised] PHST- 2013/03/18 00:00 [accepted] PHST- 2013/04/10 06:00 [entrez] PHST- 2013/04/10 06:00 [pubmed] PHST- 2013/07/19 06:00 [medline] AID - S0041-008X(13)00131-2 [pii] AID - 10.1016/j.taap.2013.03.024 [doi] PST - ppublish SO - Toxicol Appl Pharmacol. 2013 Jun 15;269(3):226-32. doi: 10.1016/j.taap.2013.03.024. Epub 2013 Apr 6.