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Evaluation of the mutagenic effects of myosmine in human lymphocytes using the HPRT gene mutation assay |
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| Authors: | JB Havla CE Hill SZ Abdel-Rahman E Richter |
| Institution: | 1. Walther Straub Institute, Department of Toxicology, Ludwig-Maximilians University, Nussbaumstrasse 26, D-80336 Munich, Germany;2. Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, Texas, USA |
| Abstract: | The minor tobacco alkaloid myosmine is implicated in DNA damage through pyridyloxobutylation similar to the tobacco-specific nitrosamines (TSNA). In contrast to TSNA, occurrence of myosmine is not restricted to tobacco. Myosmine is genotoxic to human cells in the comet assay. In this study, the mutagenic effect of myosmine was evaluated using the cloning hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene mutation assay. Four hour exposure of isolated peripheral blood lymphocytes from 14 subjects homozygous for the Leu84 wild-type of the O6-methylguanine-DNA-methyltransferase (MGMT) gene to 1 mM of myosmine increased mutant frequency from 0.73 ± 0.58 × 10−6 in control to 1.14 ± 0.89 × 10−6 lymphocytes (P < 0.05). These new data further confirm the mutagenic effects of myosmine. |
| Keywords: | CE cloning efficiency HPB 4-hydroxy-1-(3-pyridyl)-1-butanone HPRT hypoxanthine-guanine phosphoribosyltransferase MF mutation frequency MGMT O6-methylguanine-DNA-methyltransferase NNK 4-methylnitrosamino-1-(3-pyridyl)-1-butanone NNN N&prime -nitrosonornicotine POB pyridyloxobutylation O6-POB-dGuo O6-[4-(3-pyridyl)-4-oxobut-1-yl]-2&prime -deoxyguanosine NNAL 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol TSNA tobacco-specific nitrosamines |
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