The accumulation of ascorbic acid by squamous cell carcinomas of the lung and larynx is associated with global methylation of DNA

BACKGROUND. Cigarette smokers are known to have lower concentrations of cir culating ascorbic acid than nonsmokers. In contrast, there is evidence that the extracellular fluid lining of the alveolus, which comes in close conta ct with cigarette smoke, and the alveolar macrophages of smokers are enrich ed with ascorbic acid. The clinical significance of these observations is u nknown. METHODS. The authors measured the ascorbic acid concentrations and radiolab eled methyl incorporation (which is inversely related to the degree of DNA methylation in vivo) of paired samples of squamous cell carcinoma (SCC) and adjacent uninvolved mucosa of the lung and larynx (n = 22). RESULTS. Cancerous tissues had significantly higher ascorbic acid concentra tions (mean +/- standard deviation [SD, 485 +/- 77; median, 483 ng/mg prote in) compared with their matched uninvolved tissues (mean +/- SD, 151 +/- 52 ; median, 72 ng/mg protein; P < 0.0001). The radiolabeled methyl incorporat ion was significantly higher in cancerous tissues (mean +/- SD, 31,419 +/- 2629; median, 31,416 counts per minute [CPM]/mu g DNA) compared with their matched uninvolved tissues (mean +/- SD, 11,883 +/- 1567; median, 11,444 CP M/mu g DNA; P < 0.0001). The Spearman correlation between ascorbic acid con centrations and radiolabeled methyl incorporation by DNA in SCCs was invers e and statistically significant (r = -0.58, P = 0.008), indicating a benefi cial effect of accumulated ascorbic acid in global methylation of DNA. In t he uninvolved tissues, this correlation was inverse but statistically not s ignificant (r = -0.20, P = 0.35). CONCLUSIONS. Cancerous tissues of the lung and larynx demonstrated their ab ility to accumulate ascorbic acid. The accumulation of ascorbic acid by the se tissues seemed to facilitate global methylation of DNA. (C) 2000 America n Cancer Society.