Perinatal metabolism of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in C57BL mice

Journal Article · Tue May 01 00:00:00 EDT 1984 · J. Natl. Cancer Inst.; (United States)

OSTI ID:6728704

Castonguay, A; Tjaelve, H; Trushin, N; Hecht, S S

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), Journal Name: J. Natl. Cancer Inst.; (United States) Vol. 72:5; ISSN JNCIA
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AEROSOLS
ANIMALS
AUTORADIOGRAPHY
BODY
BODY AREAS
CARBON 14 COMPOUNDS
CHROMATOGRAPHY
COLLOIDS
DIGESTIVE SYSTEM
DISPERSIONS
DISTRIBUTION
FACE
FETAL MEMBRANES
FETUSES
GLANDS
HEAD
INHALATION
INTAKE
LABELLED COMPOUNDS
LIQUID COLUMN CHROMATOGRAPHY
LIVER
LUNGS
MAMMALS
MEMBRANES
METABOLITES
MICE
NITROSO COMPOUNDS
NOSE
ONTOGENESIS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PLACENTA
PREGNANCY
RESIDUES
RESPIRATORY SYSTEM
RODENTS
SEPARATION PROCESSES
SMOKES
SOLS
TISSUE DISTRIBUTION
TOBACCO SMOKES
VERTEBRATES