A study of tobacco carcinogenesis. XLII. Bioassay in A/J mice of some structural analogues of tobacco-specific nitrosamines.
The tumorigenic activities in A/J mouse lung of the tobacco-specific nitrosamines, N'-nitrosonornicotine (NNN), 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and several structural analogues were evaluated. The analogues were N-nitrosopyrrolidine (NPYR), 5'-carboxy-N'-nitrosonornicotine (CNNN), N-nitrosoproline (NPRO) and 1-(3-pyridyl)-2-buten-1-one (PBO). The results were as follows (dose in mumol per mouse/lung tumors per mouse): NNN (100/1.8 +/- 1.4); NPYR (100/3.9 +/- 1.5); CNNN (200/0.3 +/- 0.5); CNNN (100/0.5 +/- 0.6); NPRO (100/0.6 +/- 0.7); NNK (20/7.2 +/- 3.4); PBO (20/0.7 +/- 1.0); saline control (0.0.5 +/- 0.7). Several conclusions were drawn from this assay. NNK and NPYR were more tumorigenic than NNN. CNNN was non-tumorigenic and thus appears to have potential as a monitor for endogenous formation of tobacco-specific nitrosamines. The alpha,beta-unsaturated ketone PBO does not appear to be an ultimate tumorigen of NNK or NNN.
Hecht
S S
SS
American Health Foundation, Valhalla, NY 10595.
Abbaspour
A
A
Hoffman
D
D
D000236:Adenoma / Q000139:chemically induced*; D000818:Animals; D005260:Female; D008175:Lung Neoplasms / Q000139:chemically induced*; D051379:Mice; D009602:Nitrosamines / Q000378:metabolism / Q000633:toxicity*; D010947:Plants, Toxic; D013329:Structure-Activity Relationship; D014026:Nicotiana
D009602:Nitrosamines