Induction of thymomas by N-methyl-N-nitrosourea in AKR mice:Interaction between the chemical carcinogen and endogenous murine leukaemia viruses

Warren, W., Lawley, P. D., Gardner, E., Harris, G., Ball, J. K. and Cooper, C. S. ORCID: https://orcid.org/0000-0003-2013-8042 (1987) Induction of thymomas by N-methyl-N-nitrosourea in AKR mice:Interaction between the chemical carcinogen and endogenous murine leukaemia viruses. Carcinogenesis, 8 (1). pp. 163-172. ISSN 0143-3334

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Abstract

AKR mice develop thymomas spontaneously when >6 months old but when young AKR mice are treated with N-methyl-N-nitrosourea (MNU) they develop thymomas at 3-6 months of age. In this study the potential role of oncogene activation in the development of both the spontaneous and MNU-induced thymomas in AKR mice has been examined by DNA transfection into NTH3T3 mouse fibroblasts and by Southern analysis of tumour DNA. The results show that a high proportion of MNU-induced thymomas contain activated cellular rasK while no activated cellular ras genes were detected in spontaneous thymomas. Southern analysis of tumour DNA revealed that 2/30 spontaneous tumours and 2/52 MNU-induced tumours contained alterations in the c-myc gene while 5/29 spontaneous tumours and 6/56 MNU-induced tumours contained alterations in the Pim-1 gene. A more detailed analysis of the Pim-1 gene demonstrated that the alterations observed in most MNU-induced and spontaneous tumours resulted from proviral integration at the 3' end of this gene. Our analyses also demonstrated that the majority of MNU induced tumours, including those containing rearrangements in the Pim-1 gene, lacked the somatically acquired recombinant MCF proviruses that are present in most spontaneous AKR lymphomas. These results provide evidence that (i) the mechanisms of development of MNU-induced and spontaneous tumours in AKR mice are distinct and (II) the development of thymomas that contain proviral integrations at the Pim-1 locus in the MNU-treated AKR mice involve cooperation between the chemical carcinogen and endogenous murine leukaemia viruses.

Item Type: Article
Additional Information: Funding Information: We would like to thank Dr R.M.Perlmutter, Dr J.R.Jenkins, Dr W.Herr, Dr J.Adams, Dr H.T.Cuypers and Dr M.Cole for providing the cloned genes that were used as probes in this work. We also thank Helen Anton for typing the manuscript. C.S.C. was a recipient of a Special Fellowship from the Leukaemia Society of America and expresses his gratitude to Dr G.M.Cooper in whose laboratory these studies were initiated. This work was supported by grants to the Institute of Cancer Research from the Medical Research Council and the Cancer Research Campaign. J.K.B. is a Research Associate of the National Cancer Institute of Canada.
Uncontrolled Keywords: cancer research,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/1300/1306
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 18 Jul 2022 17:31
Last Modified: 02 Oct 2022 04:50
URI: https://ueaeprints.uea.ac.uk/id/eprint/86545
DOI: 10.1093/carcin/8.1.163

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