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

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.