Cytotoxic and cytostatic effects of arecoline and sodium nitrite on human cells in vitro

Arecoline, an active alkaloid of Areca catechu L., and sodium nitrite, a food additive, are highly cytotoxic and cytostatic on the Hep 2 cell line when administered in an acidic environment (pH 4.2) in the presence of S-9 mixture. Hep 2 cells (10(6)) were treated with either 0.145, 0.725 or 1.449 mM sodium nitrite or 0.042, 0.085 or 0.339 mM arecoline or sodium nitrite (0.145 mM) plus varied concentrations of arecoline (0.042, 0.085 or 0.339 mM). Their effects were additive in nature. Hep 2 cells exposed to this combination showed reduced cell survival, and lower rates of DNA and protein syntheses. Involvement of N-nitroso derivatives of arecoline is suggested to explain the results. On the basis of these studies, we speculate that N-nitroso compounds derived from arecoline can (weakly) interact with DNA.