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It has been shown that chlorosulfonyl-chloride derivatives, such as chlorosulfonylbenzoyl fluoride (CASF), can be pro-oxidant xenobiotics that can cause toxicity. This study aims to investigate whether CASF can activate the human liver cytochrome P450 (P450)2E1 and the yeast Saccharomyces cerevisiae cytochrome P450 (CYP)2E1. CASF activated P4502E1 in both yeast and human liver microsomes and was shown to be a direct-acting heme-oxygenase-1 (HO-1) inducer in both species. CASF-induced heme oxygenase activity was found to be associated with increased binding of CASF to the HO-1. This suggests that CASF activates P4502E1 via binding of CASF to the heme-binding site of P4502E1 and that CASF-induced heme-oxygenase activation is mediated through this binding site. CASF also induced over-expression of HO-1 mRNA in S. cerevisiae and human liver microsomes. Since the over-expression of HO-1 is known to increase resistance of yeast cells to CASF toxicity, this suggests that HO-1

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