TY - JOUR
T1 - 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)
AU - Sipowicz, Marek A.
AU - Amin, Shantu
AU - Desai, Dhimant
AU - Kasprzak, Kazimierz S.
AU - Anderson, Lucy M.
N1 - Funding Information:
We thank Dr Victor Nelson (SAIC Frederick, NCI-FCRDC, Frederick, MD) for synthesizing 8-oxo-dG and Lisa Birely for excellent animal care and treatment. This work was supported in part by NIH grant CA-17613.
PY - 1997/7/15
Y1 - 1997/7/15
N2 - 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 tissues. 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 treatment. 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.
AB - 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 tissues. 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 treatment. 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.
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U2 - 10.1016/S0304-3835(97)00208-5
DO - 10.1016/S0304-3835(97)00208-5
M3 - Article
C2 - 9233836
AN - SCOPUS:0030819949
SN - 0304-3835
VL - 117
SP - 87
EP - 91
JO - Cancer Letters
JF - Cancer Letters
IS - 1
ER -
