Evaluation of the Transplacental Tumorigenicity of the Tobacco-specific Carcinogen 4-(Methylnitrosamino)-l-(3-pyridyl)-l-butanone in Mice

Lucy M. Anderson, Stenhen S. Hecht, Dwavne E. Dixon, Lee F. Dove, Robert M. Kovatcfa, Shantu Amin, Dietrich Hoffmann, Jerry M. Rice

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Abstract

The transplacental tumorigenicity of the tobacco-specific carcinogen 4-(methylnitrosamino)-l -(3-pyridy 1)–1 -butanone (NNK) was assessed in three strains of mice: A/J; C3H/He x C57BL/6 F, (hereafter called C3B6F,); and Swiss outbred |Cr:NIH(S)|. NNK (100 mg/kg) was administered i.p. on Days 14,16, and 18 of gestation to A/J and C3H/He mice and on Days 15, 17, and 19 of gestation to the Swiss mice. The effects of postnatal treatment with tumor-promoting agents, including 0.05% sodium barbital in the drinking water until death or a single dose of Arodor 1254 (a mixture of polychlorinated biphenyls, PCB) given on Postnatal Day 8 or 56, were also examined. Progeny were sacrificed at age 24 wk (A/J) or 72 wk (C3B6F, and Swiss). Significant incidences of tumors occurred in the lungs of strain A/J progeny and in the livers of male G3B6F| and Swiss progeny. Lung tumor incidence was 8 of 34 (24%) in the female offspring of the A/J mice treated with NNK, compared with 1 of 39 (3%) in controls (P < 0.05). A 2-fold difference in lung tumor incidence in male offspring of NNK-treated (4 of 23,13%) versus control (3 of 48,6%) A/J mice was not of statistical significance. However, the incidence of lung tumors in NNK-exposed progeny A/J mice in both sexes combined (12 of 66, 18%) was also significantly greater than in controls (4 of 87, 5%). The incidence of liver tumors in the male C3B6F, mice exposed transplacentally to NNK was 12 of 30 (40%) compared to 8 of 46 (17%) in controls (P < 0.05). No effects of postnatal sodium barbital or PCB were observed on transplacental NNK tumorigenidty in C3B6F, mice. The combined incidence of liver carcinoma in male mice in all NNK-treated groups (13 of 141, 9%) was significantly greater (P < 0.05) than in controls (5 of 144,3%). In male Swiss mice exposed transplacentally to NNK, the incidence of liver tumors was 3 of 57 (5%) compared to 0 of 35 controls, and postnatal treatment with PCB on Day 56 caused a significant increase (5 of 26, 19%) (P < 0.05) in the incidence of NNK-induced liver tumors. The combined incidence of liver tumors in the male offspring of the Swiss mice treated with NNK, with or without PCB, was 8 of 83 (10%) which was significantly greater (P < 0.05) than in controls (0 of 66). The mothers in all NNK-treated groups of all three strains developed lung tumors in high incidence and multiplicity, and C3H mothers also presented a significant number of liver tumors. Taken together, the results of this study demonstrate that NNK is a transplacental tumorigen in the mouse, with activity that is relatively weak compared with the adult and is demonstrable only in fetal target organs of high sensitivity.

Original languageEnglish (US)
Pages (from-to)3770-3775
Number of pages6
JournalCancer Research
Volume49
Issue number14
StatePublished - Jul 15 1989

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Anderson, L. M., Hecht, S. S., Dixon, D. E., Dove, L. F., Kovatcfa, R. M., Amin, S., Hoffmann, D., & Rice, J. M. (1989). Evaluation of the Transplacental Tumorigenicity of the Tobacco-specific Carcinogen 4-(Methylnitrosamino)-l-(3-pyridyl)-l-butanone in Mice. Cancer Research, 49(14), 3770-3775.