Abstract：
:Human CYP2A6 has been recognized as being involved in the mutagenic activation of promutagens such as the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Methoxsalen (8-methoxypsoralen) was reported to inhibit CYP2A6. In the present study, the inhibitory effects of methoxsalen on NNK-induced lung tumorigenesis in female A/J mice were examined. Female A/J mice were treated with methoxsalen at doses of 50 or 12.5 mg/kg body weight, given by stomach tube, daily for 3 days. One h after the final treatment, NNK was injected i.p. at a dose of 2 mg/mouse. The experiments were terminated 16 weeks after the first methoxsalen treatment, and lung adenomas were analyzed. Pretreatment of methoxsalen significantly reduced tumor incidence from 93.8% to 16.7% (50 mg/kg) and 20.0% (12.5 mg/kg), and tumor multiplicity from 5.97 to 0.23 (50 mg/kg) and 0.25 (12.5 mg/kg) tumors/mouse. These results clearly demonstrated that methoxsalen, a potent human CYP2A6 inhibitor, is a strong chemopreventive agent against NNK-induction of lung tumorigenesis.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Takeuchi H,Saoo K,Yokohira M,Ikeda M,Maeta H,Miyazaki M,Yamazaki H,Kamataki T,Imaida Ksubject
Has Abstractpub_date
2003-11-15 00:00:00pages
7581-3issue
22eissn
0008-5472issn
1538-7445journal_volume
63pub_type
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