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Role of Ultraviolet Radiation in the Induction of Melanocytic Tumors in Hairless Mice following 7,12-Dimethylbenz(a)anthracene Application and Ultraviolet Irradiation¹

Laboratory of Molecular Dermatologic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, and Department of Dermatology, Harvard Medical School, Boston, Massachusetts 02115

We examined the role of UVR (UV radiation) (UVA, 320–400 nm; UVB, 290–320 nm; and the combination of UVA and UVB) as a promoter in the induction of cutaneous melanoma. One hundred and seventy hairless mice (Skh-hr2), 6–8 weeks old, were treated in 8 groups: group I, DMBA [7,12-dimethylbenz(a)anthracene] plus UVA; group II, DMBA plus UVA plus UVB; group III, DMBA plus UVB; group IV, DMBA; group V, UVA; group VI, UVA plus UVB; group VII, UVB; group VIII, control. DMBA (0.5% solution) was applied once to promote the formation of dermal melanocytic nevus-like lesions while UVR treatments were conducted 3 times/week for 30 weeks. The mice were examined periodically for the development of multiple pigmented lesions, papillomas, squamous cell carcinomas, melanomas, and lymphomas. Treatment with DMBA plus UVA, DMBA plus UVB, and DMBA plus UVA plus UVB stimulated the development of multiple pigmented nevus-like lesions (85–100%) in mice of groups I, II, III, and IV. Upon necroscopy, 27–33% of animals in groups I, II, and III receiving UVR treatments developed clinically and histologically characterized melanomas. Treatment with DMBA alone did not produce melanomas. DMBA-treated animals in groups I, II, and III which received UVR treatments also developed lymphomas (21–50%). Animals treated with DMBA alone or those that received UVB or the combination of UVB plus UVA (without DMBA) developed only papillomas and squamous cell carcinomas (25–47%). Skin tumors were analyzed for the presence of point mutations in the ras gene. Polymerase chain reaction amplification of DNA and selective oligonucleotide hybridization revealed mutations in the 61st codon of the N-ras gene in the precursor nevus-like lesions and melanoma samples studied. This study suggests that UVR (both UVA and UVB) plays a role as a promoter in the stimulation of melanoma and lymphoma development in hairless mice.

¹ This work was supported by the Josephine M. Lilly Memorial Melanoma Research Fund, the National Foundation for Cancer Research, and the NIH (CA24988 and CA05003).

² To whom requests for reprints should be addressed, at the Dana-Farber Cancer Institute, 44 Binney St., Boston, MA 02115.

Received 4/ 5/91. Accepted 6/24/91.

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