CYTOTOXICITY, SISTER-CHROMATID EXCHANGES AND DNA SINGLE-STRAND BREAKS INDUCED BY 4-OXO-4-(3-PYRIDYL)BUTANAL, A METABOLITE OF A TOBACCO-SPECIFIC N-NITROSAMINE

被引:12
作者
ALAOUIJAMALI, MA [1 ]
GAGNON, R [1 ]
ELALAMI, N [1 ]
CASTONGUAY, A [1 ]
机构
[1] UNIV LAVAL,SCH PHARM,CANC ETIOL & CHEMOPREVENT LAB,QUEBEC CITY G1K 7P4,QUEBEC,CANADA
来源
MUTATION RESEARCH | 1990年 / 240卷 / 01期
关键词
Aldehyde; Cytotoxicity; DNA damage; Sister-chromatid exchanges; Tobacco-specific N-nitrosamine;
D O I
10.1016/0165-1218(90)90005-M
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The tobacco-specific N-nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), is metabolized by α-carbon hydroxylation to reactive diazohydroxides and aldehydes. The aim of this study was to determine the relative ability of one NNK-derived aldehyde, 4-oxo-4-(3-pyridyl) butanal, to induce cytotoxicity, sister-chromatid exchanges (SCEs) and DNA single-strand breaks (SSBs) in V79 cells. Our data demonstrate that this aldehyde is cytotoxic for V79 cells (IC50 = 0.4 mM) and induces SCEs at concentrations ranging from 0.01 to 0.5 mM. DNA SSBs were observed at concentrations ranging from 0.05 to 1 mM and were repaired within 8 h. When V79 cells were cultured with primary hepatocytes, there was a reduction in the frequency of SCEs induced by the aldehyde. This suggests that hepatocytes can partially deactivate the aldehyde. Our results suggest that this aldehyde is one of the reactive intermediates generated during NNK metabolism. © 1990.
引用
收藏
页码:25 / 33
页数:9
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