Aldo-keto reductases protect lung adenocarcinoma cells from the acute toxicity of B[a]P-7,8-trans-dihydrodiol

摘要: Tobacco smoke exposure stimulates the expression of genes that are likely to be involved in metabolism its combustion products such as polycyclic aromatic hydrocarbons (PAH). Four induced aldo-keto reductases (AKR), enzymes metabolically activate PAH o-quinones. Alternatively, PAHs metabolized (±)-anti-diol epoxides, (±)-anti-benzo[a]pyrene diol epoxide ((±)-anti-BPDE)), by combined action P4501A1/1B1 and hydrolase. (±)-anti-BPDE forms DNA adducts directly, while o-quinones cause damage oxidative stress through a futile redox cycle. To address role AKRs cytotoxicity, we compared cytotoxicity metabolites effects overexpressing AKR1A1 lung cells. B[a]P-7,8-trans-dihydrodiol, an intermediate metabolism, toxic A549 cells at concentrations with IC50 ∼2 μM. In contrast, o-quinone B[a]P-7,8-dione was about 10-fold less cell...