Mutagen sensitivity of nasopharyngeal cancer patients

Primary nasopharyngeal carcinomas (NPCs) may be of various types, including squamous cell carcinomas, undifferentiated carcinomas, and lymphoepithelio mas. Tumor initiation has been linked to the Epstein-Barr virus and, in som e geographical regions, to alimentary factors. Possible hereditary componen ts for the appearance of NPCs have not yet been clearly identified. In this study, genetic sensitivity to the genotoxic effects of carcinogenic xenobi otics as an endogenous risk factor of tumor initiation was investigated. The single cell microgel electrophoresis assay was used to quantify chemica lly-induced DNA damage in lymphocytes of 30 NPC patients and 30 non-tumor d onors. The xenobiotics investigated were N'-nitrosodiethylamine, sodium dic hromate, and nickel sulphate, and N-methyl-N'-nitro-N-nitrosoguanidine (MNN G) and dimethyl sulfoxide (DMSO) as positive and negative controls, respect ively. The extent of DNA migration in the solvent control cultures was not signifi cantly different between the two groups (1.2 +/- 0.5 mean Olive tail moment and standard deviation of 30 individuals for NPC patients; 1.1 +/- 0.4 for non-tumor donors). With constant exposure and electrophoretic conditions, genotoxic effects of varying degrees were induced by the different xenobiot ics in tumor and non-tumor patients (nickel sulphate: 7.1 +/- 2.5 for NPC p atients and 5.9 +/- 1.6 for non-tumor donors; sodium dichromate: 18.1 +/- 5 .3 for NPC patients and 16.2 +/- 5.4 for non-tumor donors; MNNG: 47.8 +/- 1 3.3 for NPC patients and 52.7 +/- 13.6 for non-tumor donors). Only N'-nitro sodiethylamine proved to induce significantly more DNA migration in lymphoc ytes of tumor patients (9.8 +/- 3.1) as compared to non-tumor patients (8.2 +/- 2.3). Although for sodium dichromate the degree of DNA migration did n ot significantly differ, variability in migration patterns proved to be low er in the tumor group. Mutagen sensitivity of NPC patients was shown to be elevated for a selected xenobiotic, whereas a general elevation of DNA fragility was not present. Further studies on mutagen sensitivity as an endogenous risk factor influen cing the susceptibility of patients at the time of first diagnosis of nasop haryngeal carcinomas are warranted. (C) 2001 Elsevier Science B.V. All righ ts reserved.