Tumorigenicity of the tobacco-specific carcinogen 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone in infant mice

L. M. Anderson, S. S. Hecht, R. M. Kovatch, S. Amin, D. Hoffmann, J. M. Rice

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19 Scopus citations


The tobacco-specific nitrosamine, 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), is a potent carcinogen in adult rodents and variably effective transplacentally, depending on species. In pursuit of the thesis that human infants may be especially vulnerable targets for tumor initiation by tobacco smoke constituents, we tested the efficacy of NNK as a tumor initiator in infant mice. Cr: NIH(S) (NIH Swiss outbred) mice were given 50 mg/kg NNK i.p. on postnatal days 1, 4, 7, 10 and 14, with saline to controls. At an average age of 13 - 15 months, 57% of the NNK-exposed male offspring had hepatocellular tumors, with a multiplicity of 1.15 ± 1.4, including 4 with carcinoma. Liver tumors including 2 carcinomas were found in 8 (14%) of the NNK-exposed female offspring. There were no hepatocellular neoplasms in any control. A significant increase in primary lung tumors also occurred in the NNK-treated males, with an incidence of 30 55 (57%) and a multiplicity of 0.7 ± 0.2, vs. 7 33 (21%), multiplicity 0.3 ± 0.6, in controls (P < 0.025). An apparent increase in the incidence of lung tumors in NNK-treated females, 21 57 (37%) vs. 7 32 (22%) in controls, approached significance (P < 0.1). Thus NNK was a moderately potent neonatal carcinogen for liver and lung in infant Swiss mice and more efficacious in this regard than when received transplacentally by mice of the same strain.

Original languageEnglish (US)
Pages (from-to)177-181
Number of pages5
JournalCancer Letters
Issue number3
StatePublished - Jul 4 1991
Externally publishedYes

Bibliographical note

Funding Information:
The authors appreciate the expertise of Daniel Logsdon and John Carter in animal treatment and care. This work was supported in part by Grant 29580 from the National Cancer Institute.


  • 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
  • liver tumors
  • lung tumors
  • neonatal mice
  • tobacco-specific nitrosamine


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