Nature 303, 72 - 74 (05 May 1983); doi:10.1038/303072a0

Mouse skin carcinomas induced in vivo by chemical carcinogens have a transforming Harvey-ras oncogene

Allan Balmain & Ian B. Pragnell

Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK

Several groups have shown that the malignant phenotype can be transferred to NIH/3T3 fibroblasts by incorporation of DNA isolated from tumour cell lines¹⁻⁵. These studies have demonstrated that the transforming activity of DNA isolated from human bladder, lung and colon carcinoma cell lines is related to an alteration of the cellular homologues of the ras genes of Harvey or Kirsten murine sarcoma viruses⁶⁻¹¹. It is, however, unclear what relevance these observations have to the multistage nature of tumorigenesis in vivo, in which several independent events are required in both humans^12,13 and experimental animals^14,15. The activation of a cellular oncogene in a defined experimental system for the progressive induction of solid tumours has not yet been demonstrated. We report here that high molecular weight DNA from transplanted squamous cell carcinomas induced by sequential treatment of mouse skin with initiators and promoters of carcinogenesis causes morphological transformation of NIH/3T3 fibroblasts at high frequency. The transforming properties are due to the transfer of an activated cellular homologue of the Harvey-ras (ras ^H) oncogene.

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