Enhancement of the clostagenicity of N-nitrosodialkylamines plus near-ultraviolet irradiation by ethanol in Chinese hamster lung fibroblasts

Early work from our laboratory showed a synergistic action of N-nitrosodialkylamines and near-ultraviolet light (UVA, 320-400 nm) to cause mutations in bacteria and phages. Recently we reported that N-nitrosodialkylamines + UVA induces chromosome aberrations in Chinese hamster lung cells in culture. We have now found that ethanol can potentiate this clastogenic action of N-nitrosodiolkylamines + UVA. When the cells were treated with N-nitrosopyrrolidine (NPYR) or N-nitrosodiethylamine (NDEA) + UVA for 2 hours in the presence of 1% ethanol, approximately 2-fold increase in the numbers of cells with aberrant chromosomes was observed, compared to those found without the ethanol. NPYR/NDEA only, ethanol only, or ethanol + UVA did not cause the aberrations. The enhancement was dependent on the concentration of ethanol. Treatment of cells with ethanol before the NPYR + UVA was ineffective. By contrast, treatment of cells with NPYR + UVA and then with ethanol was as effective as with the simultaneous treatment. Methanol showed synergistic effects similar to those of ethanol, but mannitol did not. Intracellular hydrogen peroxide was found to be increased twofold over that in the background by a treatment with ethanol + UVA. The alcohol-mediated enhancement of the clastogenic action of N-nitrosodialkylamines + UVA may be a consequence of an increase in intracellular oxidative stress, or simply due to increased membrane permeability.