Chronic nicotine consumption does not influence 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis.
Nicotine replacement therapy is often used to maintain smoking cessation. However, concerns exist about the safety of long-term nicotine replacement therapy use in ex-smokers and its concurrent use in smokers. In this study, we determined the effect of nicotine administration on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumors in A/J mice. Female mice were administered a single dose of NNK (10 μmol) and 0.44 μmol/mL nicotine in the drinking water. Nicotine was administered 2 weeks prior to NNK, 44 weeks after NNK, throughout the experiment, or without NNK treatment. The average weekly consumption of nicotine-containing water was 15 ± 3 mL per mouse, resulting in an estimated daily nicotine dose of 0.9 μmol (0.15 mg) per mouse. Nicotine administration alone for 46 weeks did not increase lung tumor multiplicity (0.32 ± 0.1 vs. 0.53 ± 0.1 tumors per mouse). Lung tumor multiplicity in NNK-treated mice was 18.4 ± 4.5 and was not different for mice consuming nicotine before or after NNK administration, 21.9 ± 5.3 and 20.0 ± 5.4 tumors per mouse, respectively. Lung tumor multiplicity in animals consuming nicotine both before and after NNK administration was 20.4 ± 5.4. Tumor size and progression of adenomas to carcinomas was also not affected by nicotine consumption. In addition, nicotine consumption had no effect on the level of O(6)-methylguanine in the lung of NNK-treated mice. These negative findings in a commonly used model of human lung carcinogenesis should lead us to question the interpretation of the many in vitro studies that find that nicotine stimulates cancer cell growth.
Department of Biochemistry Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA. murph062@umn.edu
Sharon E
SE
Murphy
Linda B
LB
von Weymarn
Melissa M
MM
Schutten
Fekadu
F
Kassie
Jaime F
JF
Modiano
D000236:Adenoma / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002478:Cells, Cultured; D060766:Drinking Water; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008175:Lung Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008805:Mice, Inbred A; D009538:Nicotine / Q000008:administration & dosage*; D009602:Nitrosamines / Q000633:toxicity*
D002273:Carcinogens; D060766:Drinking Water; D009602:Nitrosamines; D006147:Guanine; D009538:Nicotine; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; C008449:O-(6)-methylguanine