Preferential metabolism of N-nitrosodiethylamine by two cell lines derived from human pulmonary adenocarcinomas

Journal Article · Wed Jan 01 00:00:00 EST 1986 · Carcinogenesis; (United States)

DOI:https://doi.org/10.1093/carcin/7.1.17· OSTI ID:5858954

Falzon, M; McMahon, J B; Gazdar, A F; Schuller, H M

Diethylnitrosamine (DEN), in common with other nitrosamines, is a carcinogenic agent which produces tumors in a wide variety of tissues in experimental animals. The pulmonary Clara cell is a major target of N-nitrosamine-induced carcinogenesis in hamsters and rats. DEN is believed to require metabolic activation to elicit its carcinogenic effects. The metabolism of (/sup 14/C)DEN was studied in two cell lines derived from human lung adenocarcinomas and two cell lines derived from human small cell lung cancers by monitoring /sup 14/CO/sub 2/ production and covalent binding of radiolabel from (/sup 14/C)DEN to the cell protein and DNA fractions. (/sup 14/C)DEN was metabolized by adenocarcinoma-derived NCI-H322 (with Clara cell features) and NCI-H358 (with features of alveolar type II cells) but not by NCI-H69 and NCI-H128 (derived from small cell carcinoma). Metabolism was markedly inhibited by heat denaturation of the cell protein. (/sup 14/C)DEN metabolism by NCI-H322 was greatly decreased when the incubation was carried out under anaerobic conditions and in the presence of a carbon monoxide enriched atmosphere. These results suggested the involvement of the cytochrome P-450-dependent monooxygenase enzyme system. Metabolism by NCI-H358 was also decreased in the absence of oxygen or presence of carbon monoxide although the effects were relatively small compared with the results with NCI-H322. On the other hand, aspirin or indomethacin, which are inhibitors of the fatty acid cyclooxygenase component of prostaglandin endoperoxide synthetase, preferentially inhibited (/sup 14/C)DEN metabolism by NIC-H358. There were little or no effects of these inhibitors on the metabolism of DEN in NCI-H322. The data suggest that DEN metabolism in different lung cell types may be carried out by different enzyme systems which in turn may contribute to the selective effect of DEN in the lung.

• Research Organization: National Cancer Institute, Bethesda, MD
• OSTI ID: 5858954
• Journal Information: Carcinogenesis; (United States), Vol. 1
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
59 BASIC BIOLOGICAL SCIENCES
NITROSAMINES
METABOLISM
CARBON 14 COMPOUNDS
CARBON DIOXIDE
CARCINOGENS
MAN
METABOLIC ACTIVATION
TRACER TECHNIQUES
TUMOR CELLS
AMINES
ANIMAL CELLS
ANIMALS
CARBON COMPOUNDS
CARBON OXIDES
CHALCOGENIDES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
NITROSO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OXIDES
OXYGEN COMPOUNDS
PRIMATES
VERTEBRATES
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