Mutagen sensitivity of nasopharyngeal cancer patients.
Primary nasopharyngeal carcinomas (NPCs) may be of various types, including squamous cell carcinomas, undifferentiated carcinomas, and lymphoepitheliomas. Tumor initiation has been linked to the Epstein-Barr virus and, in some geographical regions, to alimentary factors. Possible hereditary components for the appearance of NPCs have not yet been clearly identified. In this study, genetic sensitivity to the genotoxic effects of carcinogenic xenobiotics as an endogenous risk factor of tumor initiation was investigated. The single cell microgel electrophoresis assay was used to quantify chemically-induced DNA damage in lymphocytes of 30 NPC patients and 30 non-tumor donors. The xenobiotics investigated were N'-nitrosodiethylamine, sodium dichromate, and nickel sulphate, with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and dimethyl sulfoxide (DMSO) as positive and negative controls, respectively. The extent of DNA migration in the solvent control cultures was not significantly 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 xenobiotics in tumor and non-tumor patients (nickel sulphate: 7.1+/-2.5 for NPC patients 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+/-13.3 for NPC patients and 52.7+/-13.6 for non-tumor donors). Only N'-nitrosodiethylamine proved to induce significantly more DNA migration in lymphocytes 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 not significantly differ, variability in migration patterns proved to be lower 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 influencing the susceptibility of patients at the time of first diagnosis of nasopharyngeal carcinomas are warranted.
Kleinsasser
N H
NH
Department of Otolaryngology, Head and Neck Surgery, Ludwig-Maximilians-University Munich, 80336, Munich, Germany. norbert.kleinsasser@hno.med.uni-muenchen.de
Wagner
C
C
Wallner
B C
BC
Harréus
U A
UA
Kastenbauer
E R
ER
D000328:Adult; D000368:Aged; D002840:Chromates / Q000633:toxicity*; D020552:Comet Assay; D004249:DNA Damage; D004260:DNA Repair; D004052:Diethylnitrosamine / Q000633:toxicity*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009153:Mutagens / Q000633:toxicity*; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D009532:Nickel / Q000633:toxicity*
D002840:Chromates; D009153:Mutagens; D004052:Diethylnitrosamine; C029938:nickel sulfate; D009532:Nickel; C016104:sodium bichromate