Comparing the genotoxic sensitivities of human peripheral blood lymphocytes and mucosa cells of the upper aerodigestive tract using the Comet assay

Carcinogenesis in the upper aerodigestive tract is influenced by multiple f actors. Besides tobacco and alcohol consumption, specific pollutants such a s phthalates, nitrosamines, and polycyclic aromatic carbohydrates may be im portant in tumor initiation. Genetic factors related to mutagen sensitivity and DNA repair capacity also play a role. The aim of this study was to inv estigate whether human peripheral blood lymphocytes and mucosal epithelium of the upper aerodigestive tract, the target for volatile and liquid xenobi otics, are equally sensitive to genotoxic agents. The Comet assay was used to detect for DNA damage induced by genotoxic agen ts in mucosal epithelial cells and peripheral blood lymphocytes of 60 volun teers. Mucosa was harvested from larynx, oropharynx, and inferior nasal tur binates. Xenobiotics investigated were dibutylphthalate (DBP), diisobutylph thalate (DiBP), N'-nitrosodiethylamine (NDELA), benzo[a]pyrene (B[a]P), and N'-methyl-N'-nitro-N-nitrosoguanidine (MNNG). DBP, DiBP, B[a]P, NDELA and MNNG induced a significant increase in DNA migration in both cell populatio ns. Peripheral blood lymphocytes were more sensitive than mucosal cells to DBP and DiBP, but not to NDELA and B[a]P. The correlation, in terms of DNA migration, between lymphocytes and mucosal cells among volunteers was relat ively poor. Based on the poor correlation in response between the two cell types, the sensitivity of peripheral blood lymphocytes to genotoxic agents appears to be a poor predictor of sensitivity in the target cells of the up per aerodigestive tract. Further attention should be focused on intra-indiv idual mutagen sensitivities and inter-individual genetic differences as reg ards susceptibility to upper aerodigestive tract cancer. (C) 2000 Elsevier Science B.V. All rights reserved.