Inter-individual variation of smoking-related DNA adducts in lymphocytes-relationship to mRNA levels for CYP1A1 and DNA repair enzymes

Abstract

The measurement of DNA adducts is a useful indicator for environmental carcinogen exposure monitoring. To clarify the effect of metabolic activation and DNA repair system on the inter-individual variation of DNA adduct levels, aromatic DNA adducts and mRNA expression of metabolic and repair enzymes were measured in 43 human lymphocytes. Aromatic DNA adducts were measured by the nuclease P1 postlabelling method. The metabolic activation enzyme; cytochrome P4501A1 (CYPIA1), and the repair enzyme; excision repair cross complimenting gene (ERCC1), and the xeroderma pigmentosum C group cell gene (XPCC), mRNA expression were measured by the reverse transcription-PCR method. The mean adduct levels were 1.01 ± 0.49 in 43 subjects. There was a positive correlation between DNA adducts and CYP1A1 mRNA (r = 0.33, p = 0.12). DNA adduct levels had a positive correlation with ERCC1 (r = 0.35, p = 0.03) and a negative correlation with XPCC mRNA levels (r = –0.28, p = 0.07). We found Brinkman index, CYP1A1 genotypes, CYP1A1 mRNA and XPCC mRNA as a predictor for log DNA adduct levels in multivariate analysis. Metabolic activation and the repair system may explain the inter-individual variation of DNA adducts in lymphocytes.

Keywords::

• Dna Adduct Repair