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ras Oncogenes and Phenotypic Staging in N-Methylnitrosourea- and -Irradiation-induced Thymic Lymphomas in C57BL/6J Mice¹

Department of Pathology and Kaplan Cancer Center, New York University Medical Center, New York, New York 10016

We have investigated stages of thymic lymphoma development in radiation and N-methylnitrosourea (NMU)-treated C57BL/6J mice. The lymphoma cell was identified serologically as a cortical population bearing MEL-14^hi, H-2K^hi, and IL-2R⁺ surface markers. According to these parameters in C57BL/6J mice the lymphoma cell was the same regardless of inducing agent or activated oncogene (ras or non-ras). Transforming activity in the radiation and NMU-induced tumors was analyzed using both the nude mouse tumorigenicity assay and the focus-forming assay. 8/10 NMU-induced tumors and 12/15 radiation-induced tumors showed transforming activity in the tumorigenicity assay. Southern blot analysis of the nude mouse transformants demonstrated K-ras transforming sequences in eight of eight NMU-induced lymphoma DNAs, two of 12 radiation-induced lymphoma DNAs and N-ras transforming sequences in five of 12 radiation-induced lymphoma DNAs. The non-ras transforming activity in five DNAs from radiation-induced thymic lymphomas indicates the presence of an unidentified oncogene(s) in these tumors. Staging of thymic lymphoma development in this animal model system will allow the study of oncogene activation early in the course of carcinogen-induced disease. These results also emphasize the high sensitivity of the nude mouse assay to score for activated oncogenes and might also indicate a high frequency of K-ras activation in NMU-induced lymphomas in C57BL/6J mice.

¹ Supported by Public Health Service Grants CA40533 and AI23276 and National Institutes of Health Grants CA36327, CA16239, and ES03847.

² To whom requests for reprints should be addressed, at Department of Pathology and Kaplan Cancer Center, New York University Medical Center, 550 First Avenue, New York, NY 10016.

³ Present Address: Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461.

⁴ Recipient of a Leukemia Society of America Scholar Award.

Received 3/25/88. Revised 6/23/88. Accepted 7/ 5/88.

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