Formation of genotoxic products from N-nitrosoheptamethyleneimine (NHMI), 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone (NNK) and N′-Nitrosonornicotine (NNN) by isolated rabbit lung cells
✍ Scribed by Jon E. Dahl; Rune Becher; Marit Låg; Hildegard M. Schuller; Erik Dybing
- Publisher
- Springer
- Year
- 1990
- Tongue
- English
- Weight
- 692 KB
- Volume
- 6
- Category
- Article
- ISSN
- 0742-2091
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✦ Synopsis
The genotoxic potentials of N-nitrosoheptamethyleneimine (NHMI), 4-(methylnitrosamino)-l-(3-p yridyl)-l-butanone (NNK)
and N'-nitrosonornicotine (NNN) were studied in fresh preparations of Clara cells and type H cells isolated by centrifugal elutriation and density gradient centrifugation, and macrophages from rabbit lung. The activation of the compounds to bacterial mutagens was assayed in the Salmonella mutagenicity test using strains of TA 100 and TA 1530 preincubated with test chemicals and cells placed in chambers with nucleopore membranes to separate cells and bacteria. Unscheduled DNA synthesis was measured by incorporation of [3H_~thymidine in the cells after exposure to the compounds. NHMI, N N K and N N N were not activated to bacterial mutagens by Clara cells, type H cells or macrophages, presumably because the reactive metabolites generated were not released into the incubation medium. However, N H M I and N N K increased unscheduled DNA synthesis in Clara cells, and the highest repair activity was found after incubation with NNK. The effect of N N N