Hostname: page-component-586b7cd67f-t7fkt Total loading time: 0 Render date: 2024-11-28T04:39:55.277Z Has data issue: false hasContentIssue false
  • English
  • Français

At least four genes and sex are associated with susceptibility to urethane-induced pulmonary adenomas in mice

Published online by Cambridge University Press:  14 April 2009

Michael F. W. Festing ,
Aili Yang  and
A. M. Malkinson
Michael F. W. Festing*
Affiliation:
MRC Toxicology Unit, University of Leicester, Hodgkin Building, PO Box 138, Lancaster Road, Leicester LE1 9HN, UK
Aili Yang
Affiliation:
MRC Toxicology Unit, University of Leicester, Hodgkin Building, PO Box 138, Lancaster Road, Leicester LE1 9HN, UK
A. M. Malkinson
Affiliation:
Department of Pharmaceutical Sciences, School of Pharmacy, Campus Box C238, 4200 East Ninth Avenue, Denver, Colorado 80262, USA
*
* Corresponding author.
Rights & Permissions [Opens in a new window]

Summary

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Susceptibility to urethane-induced lung adenomas in mice has a polygenic mode of inheritance, with no obvious discontinuity in lung tumour counts among 37 AXB recombinant inbred strains. However, mean tumour counts were markedly higher in strains carrying the A/J allele at the Kras2 and H2 complex than in those carrying the C57BL/6 allele. In 162 F2 hybrids and small numbers of both backcrosses between strain A/J (susceptible) and C57BL/6 (resistant) mice, five factors influencing susceptibility were identified. Variation due to the ‘major’ Kras2 locus (chromosome 6) accounted for 60% of the total variation. ‘Minor’ loci linked to microsatellite markers Tnfb (in the H2 complex), D9Mit11 and D19MH16 (on chromosomes 17, 9 and 19, respectively) accounted for a further 13% of the variation, and males had more tumours than females with sex differences accounting for 2% of the variation. No significant association with 32 other loci was detected. On a square-root transformed scale, heterozygotes at all marker loci were of intermediate susceptibility compared with homozygotes. Thethree minor loci and sex only affected lung tumour counts when at least one susceptible Kras2 allele was present.

Type
Research Article
Information
Genetics Research , Volume 64 , Issue 2 , October 1994 , pp. 99 - 106
Copyright
Copyright © Cambridge University Press 1994

References

Bloom, J. L. & Falconer, D. S. (1964). A gene with major effect on susceptibility to induced lung tumours in mice. Journal of the National Cancer Institute 33, 607–618.Google ScholarPubMed
Bronner, C. E., Baker, S. M., Morrison, P. T., Warren, G., Smith, L. G., Lescoe, M. K., Kane, M., Earabino, C., Lipford, J., Lindblom, A., Tannergard, P., Bollag, R. J., Godwin, A. R., Ward, D. C., Nordenskjold, M., Fishel, R., Kolodner, R. & Liskay, R. M. (1994). Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature 368, 258–261.CrossRefGoogle ScholarPubMed
den Engelse, L., Oomen, L. C. J. M., van der Valk, M. A., Hart, A. A. M., Dux, A. & Emmelot, P. (1981). Studies on lung tumours. V. Susceptibility of mice to dimethylnitrosamine-induced tumour formation in relation to H2 haplotype. International Journal of Cancer 28, 199–208.CrossRefGoogle Scholar
Devereux, T. R., Wiseman, R. W., Kaplan, N., Foley, J. F., White, C. M., Anna, C., Watson, M. A., Patel, A., Jarchow, S., Maronpot, R. R. & Anderson, M. W. (in the Press). Assignment of a locus for murine pulmonary adenoma susceptibility to proximal chromosome 19. Mammalian Genome.Google Scholar
Dietrich, W., Katz, H., Lincoln, S. E., Shin, H.-S., Friedman, J., Dracopoli, N. C. & Lander, E. (1992). A genetic map of the mouse suitable for typing intraspecific crosses. Genetics 131, 423–447.CrossRefGoogle ScholarPubMed
Don, R. H., Cox, P. T., Wainwright, B. J., Baker, K. & Mattick, J. S. (1991). ‘Touchdown’ PCR to circumvent spurious priming during gene amplification. Nucleic Acids Research 19, 4008.CrossRefGoogle ScholarPubMed
Droms, K. A., Fernandez, C. A., Thaete, L. G. & Malkinson, A. M. (1988). Effects of adrenalectomy and corticosterone administration on mouse lung tumour susceptibility and histogenesis. Journal of the National Cancer Institute 80, 365–369.CrossRefGoogle ScholarPubMed
Falconer, D. S. & Bloom, J. L. (1962). A genetic study of induced lung tumours in mice. British Journal of Cancer 16, 665–685.CrossRefGoogle ScholarPubMed
Faraldo, M. J., Dux, A., Muhlbock, O. & Hart, G. (1979). Histocompatibility genes (the H2 complex) and susceptibility to spontaneous lung tumours in mice. Immunogenetics 9, 383–404.CrossRefGoogle Scholar
Gariboldi, M., Manenti, G., Canzian, F., Falvella, F. S., Radice, M. T., Pierotti, M. A., Porta, G. Delia, Binelli, G. & Dragani, T. A. (1993). A major susceptibility locus to murine lung carcinogenesis maps on chromosome 6. Nature Genetics 3, 132–136.CrossRefGoogle Scholar
Green, M. C. (1989). Catalog of mutant genes and polymorphic loci. In Genetic Variants and Strains of the Laboratory Mouse, 2nd edn (ed. Lyon, M. F. and Searle, A. G.), pp. 12–403. Oxford University Press.Google Scholar
Hearne, C. M., McAleer, M. A., Love, J. M., Aitman, T. J., Cornall, R. J., Ghosh, S., Knight, A. M., Prins, J.-B. & Todd, J. A. (1991). Additional microsatellite markers for mouse genome mapping. Mammalian Genome 1, 273–282.CrossRefGoogle ScholarPubMed
Lander, E. S. & Botstein, D. (1989). Mapping Mendelian factors underlying quantitative traits using RFLP linkage maps. Genetics 121, 185–199.CrossRefGoogle ScholarPubMed
Love, J. M., Knight, A. M., McAleer, M. A. & Todd, J. A. (1990). Towards construction of a high resolution map of the mouse genome using PCR-analysed microsatellites. Nucleic Acids Research 18, 4123–4130.CrossRefGoogle ScholarPubMed
Malkinson, A. M. (1991). Genetic studies on lung tumor susceptibility and histogenesis in mice. Environmental Health Perspectives 93, 149–159.CrossRefGoogle ScholarPubMed
Malkinson, A. M., Nesbitt, M. N. & Skamene, E. (1985). Susceptibility to urethane-induced pulmonary adenomas between A/J and C57BL/6J mice: use of AXB and BXA recombinant inbred lines indicating a three-locus genetic model. Journal of the National Cancer Institute 75, 971–974.CrossRefGoogle Scholar
Maronpot, R. R., Witschi, H. P., Smith, L. H. & McCoy, J. L. (1983). Recent experience with the strain A mouse pulmonary adenoma bioassay. Environmental Science and Research 27, 341–349.Google Scholar
Marshall, J. D., Mu, J.-L., Cheah, Y.-C., Nesbitt, M. N., Frankel, W. N. & Paigen, B. (1992). The AXB and BXA set of recombinant inbred mouse strains. Mammalian Genome 3, 669–680.CrossRefGoogle ScholarPubMed
Miyashita, N. & Moriwaki, K. (1987). H-2 controlled genetic susceptibility to pulmonary adenomas induced by urethane and 4-nitroquinoline 1-oxide in A/Wy congenic strains. Japanese Journal of Cancer Research (Gann) 78, 494–498.Google Scholar
Nesbitt, M. N. & Skamene, E. (1984). Recombinant inbred mouse strains derived from A/J and C57BL/6J: a tool for the study of genetic mechanisms in host resistance to infection and malignancy. Journal of Leukocyte Biology 36, 357–364.CrossRefGoogle Scholar
Ohmori, H., Abe, T., Hirano, H., Murakami, T., Katoh, T., Gotoh, S., Kido, M., Kuroiwa, A., Nomura, T. & Higashi, K. (1992). Comparison of Ki-ras gene mutation among simultaneously occurring multiple urethaneinduced lung tumors in individual mice. Carcinogenesis 13, 851–855.CrossRefGoogle Scholar
Oomen, L. C. J. M., Valk, M. A., Hart, A. A. & Demant, P. (1989). Glucocorticoid effect on transplacental carcinogenesis and lung differentiation: influence of Histocompatibility-2 complex. Journal of the National Cancer Institute 81, 512–517.CrossRefGoogle ScholarPubMed
Papadopoulos, N., Nicolaides, N. C., Wei, Y.-F., Ruben, S. M., Carter, K. C., Rosen, C. A., Haseltine, W. A., Fleischmann, R. D., Fraser, C. M., Adams, M. D., Venter, J. C., Hamilton, S. R., Peterson, G. M., Watson, P., Lynch, H. T., Peltomaki, P., Mecklin, J.-P., Chapelle, A. de la, Kinzler, K. W. & Vogelstein, B. (1994). Mutation of a mutL homolog in hereditary colon cancer. Science 263, 1625–1628.CrossRefGoogle ScholarPubMed
Ryan, J., Barker, P. E., Nesbitt, M. N. & Ruddle, F. H. (1987). KRAS2 as a genetic marker for lung tumor susceptibility in inbred mice. Journal of the National Cancer Institute 79, 1351–1357.Google ScholarPubMed
Smith, G. S., Walford, R. L. & Mickey, R. M. (1973). Lifespan and incidence of cancer and other diseases in selected long-lived inbred mice and their Fx hybrids. Journal of the National Cancer Institute 50, 1195–1213.CrossRefGoogle Scholar
Stoner, G. D. & Shimkin, M. B. (1985). Lung tumors in strain A mice as a bioassay for carcinogenicity. In Handbook of Carcinogenesis Testing (ed, Milman, H. and Weisburger, E. K.), pp. 179–214. Park Ridge, N. J.: Noyes Publications.Google Scholar
You, M., Candrian, U., Maronpot, R., Stoner, G. & Anderson, M. (1989). Activation of the K-ras protooncogene in spontaneously occurring and chemicallyinduced lung tumours of the strain A mouse. Proceedings of the National Academy of Sciences, USA 86, 3070–3074.CrossRefGoogle Scholar
You, M., Wang, Y., Stoner, G., You, L., Maronpot, R., Reynolds, S. H. & Anderson, M. (1992). Parental bias of Ki-ras oncogenes detected in lung tumors from mouse hybrids. Proceedings of the National Academy of Sciences, USA 89, 5804–5808.CrossRefGoogle ScholarPubMed