Does the bleomycin sensitivity assay express cancer phenotype?
The bleomycin (BLM) sensitivity assay has been associated with the measuring of increased risk of individual susceptibility to cancer, when chromatid breaks per cell (b/c) induced by an in vitro treatment of lymphocytes with BLM are elevated. The high heritability of BLM sensitivity indicates a genetic background. We wished to clarify whether the test characterizes the head and neck cancer phenotype as compared not only with healthy individuals, but also with alcoholic patients (ALCs) whose exposure to tobacco and alcohol consumption were similar to that of head and neck cancer patients (HNCPs), but whose liver diseases were not cancerous. If the BLM test quantifies merely cancer susceptibility on an inherited basis, the mutagen sensitivity of HNCPs should differ from that of ALCs. Conventional chromosome analysis and the BLM assay were carried out on 156 HNCPs, 51 ALCs, 146 healthy non-smokers and non-drinkers and 149 non-drinking smokers. The spontaneous rates of chromosomal aberrations (CAs) in HNCPs, ALCs and healthy smokers were identical (2.8%), but differed significantly from the non-smoking controls (2.25%). Sporadic CAs were clearly associated with tobacco smoking, but not with health status. Mutagen sensitivity measured by the BLM test showed significantly (P < 0.04) elevated values not only in HNCPs (1.13 b/c), but also in ALCs (1.29 b/c) as compared with the controls (1.01 b/c). The main finding of the study was that a considerable proportion (46%) of Hungarian controls were mutagen sensitive, twice as many as in those populations reported by others so far. Our data suggest that the BLM test does not characterize susceptibility to cancer due to insignificant differences between HNCPs and ALCs (P = 0.12) under our conditions. However, the assay might be used as a biomarker to predict cancer susceptibility under circumstances when aberrant cell frequency is >or=2% and b/c is >or=1.
Székely
Gábor
G
Department of Oncocytogenetics and Department of Head and Neck Surgery, National Institute of Oncology, Ráth Gy. u. 7-9, H-1122 Budapest, Hungary.
Remenár
Eva
E
Kásler
Miklós
M
Gundy
Sarolta
S
D000328:Adult; D000437:Alcoholism / Q000150:complications / Q000235:genetics / Q000378:metabolism; D001761:Bleomycin / Q000494:pharmacology*; D002478:Cells, Cultured / Q000187:drug effects / Q000648:ultrastructure; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000187:drug effects*; D004351:Drug Resistance / Q000235:genetics*; D005234:Fatty Liver / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D006258:Head and Neck Neoplasms / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D006814:Hungary; D008108:Liver Diseases, Alcoholic / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000648:ultrastructure; D008297:Male; D008875:Middle Aged; D009152:Mutagenicity Tests; D009153:Mutagens / Q000494:pharmacology*; D010641:Phenotype; D012907:Smoking / Q000235:genetics / Q000378:metabolism; D013695:Temperance
D009153:Mutagens; D001761:Bleomycin