Genotoxic effects of myosmine in human lymphocytes and upper aerodigestive tract epithelial cells

Myosmine, 3-(1-pyrroline-2-yl)pyridine, is an alkaloid found in tobacco plants. Recently, it was also detected in various edibles and staple foods. Whereas other tobacco alkaloids such as nicotine and nornicotine and their nitrosation products, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN), have been widely discussed, the mutagenic impact of myosmine has not been investigated in detail. In the present study, possible genotoxic effects of myosmine were studied in human lymphocytes and nasal mucosal cells using the alkaline single cell microgel electrophoresis (Comet) assay. DNA single strand breaks, alkali labile sites and incomplete excision repair sites were expressed using the Olive tail moment (OTM). One hour incubation with myosmine at 0, 5, 10, 25 and 50 mM induced a low but significantly dose-dependent increase of DNA migration from 1.29 +/- 0.13 to 18.25 +/- 1.59 (OTM, mean +/- S.E., N=11) in lymphocytes. In nasal mucosal cells a similar although somewhat less extensive DNA damage from 1.17 +/- 0.12 to 21.67 +/- 2.97 (OTM, mean +/- S.E., N=10-11) was obtained after 1 h incubation with myosmine at 0, 10, 25, 50 and 100 mM. After prolonged incubation of human lymphocytes with 10mM myosmine for 1, 3, 6, and 24 h, a significant time-dependent increase of DNA migration from 3.45 +/- 0.43 to 57.77 +/- 8.24 (OTM, mean +/- S.E., N=4) was observed. Our data indicate that myosmine expresses significant genotoxic effects in human target cells of carcinogenesis. This result warrants further investigations on the impact of this dietary component on human health.