Possible mycological etiology of oral mucosal cancer: catalytic potential of infecting Candida aibicans and other yeasts in production of N-nitrosobenzylmethylamine

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Abstract
Yeasts were isolated from 12 cases of oral precancerous lesions (leukoplakia and erythroleukoplakia) by sampling the lesion as well as normal mucosa of each patient, yielding 21 strains of Candida albicans belonging to 15 biotypes, two strains of C. tropicalis, one strain of C. parapsilosis and two strains of Torulopsis glabrata. Biopsies were obtained from the lesions for histologic examination. The catalytic potential of the yeast strains to form N-nitrosobenzylmethylamine (NBMA) from the precursors N-benzylmethylamine and nitrite was assessed at pH 6.8. The NBMA produced was identified and quantitated by h.p.l.c. and confirmed by g.c.-m.s. Nitrosation rates were calculated as total nitrosamine subtracted the chemically produced nitrosamine, and related to number of yeast cells. The yeast strains differed in nitrosation potential (P < 0.001), ranking from 0 to 1.2 μg NBMA/106 cells. Candida albicans strains, belonging to the biotypes 051, 147, 151, 153, 157 and 353, which constitute more rarely occurring biotypes, exhibited the highest nitrosation potential. Candida tropicalis, C. parapsilosis and T. glabrata were ranked lower. Strains with high nitrosation potential were generally isolated from lesions with more advanced precancerous changes. The yeast cells were present in the superficial part of the epithelium of the lesions as branching mycelium, and in some cases extending from the mucosal surface to the deeper epithelial cell layers. This might represent a fungal transportation system which could channel precursors in the saliva at the mucosal surface to the deeper part of the epithelium where the produced nitrosamine could be deposited. Thus, further evidence is provided supporting the hypothesis that certain strains of C. albicans and of other yeasts play a causal role in the development of oral cancer, by means of endogenous nitrosamine production.