Perinatal metabolism of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in C57BL mice
Whole-body autoradiography of pregnant C57BL mice given iv injections of carbonyl-/sup 14/C-labeled 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) revealed that some metabolites were covalently bound to cellular macromolecules of the nasal mucosae, bronchial mucosae, and liver of the mother. Unbound metabolites were present in those tissues and were also localized in the gastrointestinal lumens, kidneys, urinary bladder, eye melanin, and corpora lutea of the ovaries. Autoradiograms taken at the 1-hour survival interval showed labeling of the fetal kidneys and urinary bladder. At the 4-hour survival interval, the amniotic fluid was strongly labeled. Chromatography of extracts of tissues obtained from pregnant mice on days 13 and 18 of gestation indicated that unchanged NNK and 4-(methylnitrosamino)-1-(3-pyridyl)butan-1-ol (NNAI) were present in the placentas and fetal tissues. Some NNK metabolites were covalently bound to tissues of the nose, lung, and liver of 18-day-old fetuses. These results indicate that NNK and NNAI have the capacity to cross the placental barrier and to be activated in fetal tissues. Nasal, pulmonary, and hepatic tissues of 16- and 18-day-old fetuses incubated in vitro with NNK metabolized NNK and NNAI by alpha-carbon hydroxylation. These pathways lead to intermediates able to alkylate cellular macromolecules. The nasal tissues had a higher capacity to alpha-carbon hydroxylate NNK than did pulmonary or hepatic tissues during the last stage of fetal development and during all stages of postnatal life. These results suggest that exposure of C57BL mice to NNK during the last stage of fetal development or during neonatal life could possibly result in development of tumors.
- Research Organization:
- Division of Chemical Carcinogenesis, Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, NY
- OSTI ID:
- 6728704
- Journal Information:
- J. Natl. Cancer Inst.; (United States), Vol. 72:5
- Country of Publication:
- United States
- Language:
- English
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NITROSO COMPOUNDS
METABOLITES
TISSUE DISTRIBUTION
AUTORADIOGRAPHY
CARBON 14 COMPOUNDS
FETUSES
INHALATION
LIQUID COLUMN CHROMATOGRAPHY
LIVER
LUNGS
MICE
NOSE
ONTOGENESIS
PLACENTA
PREGNANCY
TOBACCO SMOKES
AEROSOLS
ANIMALS
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BODY AREAS
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COLLOIDS
DIGESTIVE SYSTEM
DISPERSIONS
DISTRIBUTION
FACE
FETAL MEMBRANES
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HEAD
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MAMMALS
MEMBRANES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
RESIDUES
RESPIRATORY SYSTEM
RODENTS
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550501* - Metabolism- Tracer Techniques