title: Failure of cigarette smoke to induce or promote lung cancer in the A/J mouse.
abstract: A six-month bioassay in A/J mice was conducted to test the hypothesis that chronically inhaled mainstream cigarette smoke would either induce lung cancer or promote lung carcinogenicity induced by the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Groups of 20 female A/J mice were exposed to filtered air (FA) or cigarette smoke (CS), injected with NNK, or exposed to both CS and NNK. At 7 weeks of age, mice were injected once with NNK; 3 days later, they were exposed to CS for 6 h/day, 5 days/week, for 26 weeks at a mean 248 mg total particulate matter/m3 concentration. Animals were sacrificed 5 weeks after exposures ended for gross and histological evaluation of lung lesions. No significant differences in survival between exposure groups was observed. A biologically significant level of CS exposure was achieved as indicated by CS-induced body weight reductions, lung weight increases, and carboxyhemoglobin levels in blood of about 17%. Crude tumor incidences, as determined from gross observation of lung nodules, were similar between the CS-exposed and FA groups, and the NNK and CS + NNK groups. Incidences in either of these latter groups were greater than either the CS or FA groups. Furthermore, tumor multiplicity in tumor-bearing animals was not significantly different among any of the three groups (FA, NNK, CS + NNK) in which tumors were observed. Thus, CS exposure neither induced lung tumors nor promoted NNK-induced tumors. Because the CS exposure concentration was probably near the maximally tolerable level, longer exposures should be evaluated to potentially establish a CS-induced model of lung carcinogenesis in the A/J mouse.
authors.affiliation: Inhalation Toxicology Research Institute, Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM 87185-5890, USA. gfinch@lucy.tli.org.
authors.forename: G L
authors.initials: GL
authors.lastname: Finch
authors.forename: K J
authors.initials: KJ
authors.lastname: Nikula
authors.forename: S A
authors.initials: SA
authors.lastname: Belinsky
authors.forename: E B
authors.initials: EB
authors.lastname: Barr
authors.forename: G D
authors.initials: GD
authors.lastname: Stoner
authors.forename: J F
authors.initials: JF
authors.lastname: Lechner
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight; D002263:Carboxyhemoglobin / Q000378:metabolism; D002273:Carcinogens; D005260:Female; D008168:Lung / Q000033:anatomy & histology / Q000473:pathology; D008175:Lung Neoplasms / Q000139:chemically induced / Q000473:pathology*; D051379:Mice; D008805:Mice, Inbred A; D009602:Nitrosamines; D009929:Organ Size; D012016:Reference Values; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D016019:Survival Analysis
chemical_list: D002273:Carcinogens; D009602:Nitrosamines; D012906:Smoke; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D002263:Carboxyhemoglobin