OXIDATIVE DNA-DAMAGE IN TISSUES OF PREGNANT FEMALE MICE AND FETUSES CAUSED BY THE TOBACCO-SPECIFIC NITROSAMINE, 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE (NNK)
Ma. Sipowicz et al., OXIDATIVE DNA-DAMAGE IN TISSUES OF PREGNANT FEMALE MICE AND FETUSES CAUSED BY THE TOBACCO-SPECIFIC NITROSAMINE, 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE (NNK), Cancer letters, 117(1), 1997, pp. 87-91
The tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-
1-butanone (NNK), induces the promutagenic oxidative-damage DNA lesion
, 8-oxo-2'-deoxyguanosine (8-oxo-dG), in adult animals. To investigate
whether this alteration occurs in DNA after transplacental exposure,
pregnant Swiss mice were administered single or multiple doses of NNK.
The 8-oxo-dG was quantified in placenta, and maternal and fetal tissu
es. In maternal lungs, single and multiple doses of NNK significantly
increased levels of 8-oxo-dG by 23% and 32%, respectively. In maternal
liver, a significant 38% increase was observed after multiple dose tr
eatment. In the fetuses, a significant 45% increase in 8-oxo-dG levels
was observed in liver after multiple doses of NNK. This is the first
demonstration of oxidative DNA damage after transplacental exposure to
NNK, and supports the concept of maternal smoking as a contributor to
the development of childhood cancer. (C) 1997 Elsevier Science Irelan
d Ltd.