Role of ultraviolet radiation in the induction of melanocytic tumors in hairless mice following 7,12-dimethylbenz(a)anthracene application and ultraviolet irradiation.

in Cancer research by Z Husain, M A Pathak, T Flotte, M M Wick

TLDR

  • UV radiation (UVA and UVB) promotes the development of melanoma and lymphoma in hairless mice, suggesting a potential link to human skin cancer.

Abstract

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.

Overview

  • The study examines the role of UV radiation (UVA, UVB, and combination) as a promoter in the induction of cutaneous melanoma in hairless mice.
  • One hundred and seventy hairless mice (Skh-hr2) were divided into eight groups and treated with different combinations of DMBA and UVR.
  • The primary objective of the study is to investigate the association between UV radiation and the development of melanoma and lymphoma in hairless mice.

Comparative Analysis & Findings

  • Treatment with DMBA plus UVA, DMBA plus UVB, and DMBA plus UVA plus UVB stimulated the development of multiple pigmented nevus-like lesions in 85-100% of mice.
  • UVR treatments increased the development of melanomas (27-33%) and lymphomas (21-50%) in mice receiving DMBA, whereas DMBA alone did not produce melanomas.
  • Point mutations in the ras gene (61st codon of the N-ras gene) were detected in precursor nevus-like lesions and melanoma samples, suggesting a role for UVR in melanoma development.

Implications and Future Directions

  • The study suggests that UV radiation, particularly UVA and UVB, may play a role as a promoter in the development of melanoma and lymphoma in human skin.
  • Future studies should aim to investigate the mechanisms by which UVR induces point mutations in the ras gene and to determine the potential impact of UV radiation on melanoma development in human populations.
  • The findings of this study may have important implications for the prevention and treatment of melanoma and lymphoma, particularly in individuals with a history of UV exposure.
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