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Retinoid and Ethanol-Sensitive Benzo(α)Pyrene Induction of Cytochrome P450 in Human Keratinocytes

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DOI: 10.4236/jct.2012.36141    2,720 Downloads   4,125 Views   Citations

ABSTRACT

Polycyclic aromatic hydrocarbons (PAHs) induce cytochrome P-450 monoxygenase enzymes that catalyze the formation of DNA adducts. We investigated the effects benzo(α)pyrene (B[α]P) alone or in combination with ethanol on normal human keratinocyte (NHK) growth, induction of cytochrome P-4501A1 (CYP1A1), and modulation of these treatments by retinoic acid (RA) in a serum-free culture medium. Growth-arrested confluent NHK serum-free cultures were treated with B[α]P alone or in combination with ethanol and RA. The effects on CYP1A1 enzyme activity were investigated. B[α]P treatment alone was not toxic to post-confluent cells; sub-toxic ethanol stimulated cell growth regardless B[α]P treatment. No CYP1A1 activity was detected in control or ethanol-treated NHK cell cultures. B[α]P alone induced CYP1A1 activity, and B[α]P plus ethanol treatment further enhanced B[α]P-induced CYP1A1 activity. Pretreatment with all-trans-RA (t-RA) abolished ethanol enhancement of CYP1A1 activity. There is a synergistic action of ethanol in combination with PAH on induction of P-450 cytochrome enzymes. By contrast, RA reverses ethanol enhancement implying a role for retinoid therapy in counteracting the risk posed by combined alcohol and PAH exposure on epidermal cell carcinogenesis.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

J. Wille and J. Park, "Retinoid and Ethanol-Sensitive Benzo(α)Pyrene Induction of Cytochrome P450 in Human Keratinocytes," Journal of Cancer Therapy, Vol. 3 No. 6, 2012, pp. 1080-1085. doi: 10.4236/jct.2012.36141.

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