Failure of cigarette smoke to induce or promote lung cancer in the A/J mouse

Cancer Lett. 1996 Feb 6;99(2):161-7. doi: 10.1016/0304-3835(95)04059-5.


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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Body Weight
  • Carboxyhemoglobin / metabolism
  • Carcinogens
  • Female
  • Lung / anatomy & histology
  • Lung / pathology
  • Lung Neoplasms / chemically induced
  • Lung Neoplasms / pathology*
  • Mice
  • Mice, Inbred A
  • Nitrosamines
  • Organ Size
  • Reference Values
  • Smoke / adverse effects*
  • Smoking / adverse effects*
  • Survival Analysis


  • Carcinogens
  • Nitrosamines
  • Smoke
  • 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone
  • Carboxyhemoglobin