The etiology of sunlight-induced melanoma in Xiphophorus hybrid fish.
In contrast to sunlight-induced squamous cell carcinoma the etiology of cutaneous malignant melanoma (CMM) is not well understood. In particular, the role that sunlight exposure and DNA damage play in the initiation of this deadly form of cancer is an open question. Early UV carcinogenesis studies in the Xiphophorus backcross hybrid fish model by Richard Setlow indicated that direct DNA damage caused by exposure to the UVB component of sunlight is necessary and sufficient for melanoma formation. Subsequent studies by Setlow suggested that monochromatic UVA radiation that is not directly absorbed by DNA was also sufficient for melanoma induction in Xiphophorus and was, indeed, primarily responsible for initiating human melanoma. These results had significant public health consequences, suggesting that although sunscreens may inhibit UVB-induced erythema they may actually increase exposure to the UVA wavelengths that cause cancer. An intensive worldwide public debate on sunscreen use and "abuse" ensued. Our data do not support a major role of free radical chemistry in melanoma induction. We find evidence that the direct damage caused by the absorption of UVB wavelengths by DNA (e.g., the cyclobutane pyrimidine dimer or CPD) is required for CMM formation and that the ability to repair these lesions plays a significant role in tumor susceptibility. Using the Xiphophorus backcross hybrid fish we are currently in the process of re-evaluating the wavelength- and DNA damage-dependence of UV-induced melanoma and the role nucleotide excision repair and the genes controlling DNA repair and the UV response play in melanoma resistance. From these studies we hope to define the effective solar wavelength boundaries of melanoma, identify the class of critical DNA damage and elucidate the role of DNA repair in tumor suppression.
Mitchell
David
D
Department of Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park/Research Division, Smithville, Texas 78602, USA.
Paniker
Lakshmi
L
Sanchez
Guillermo
G
Trono
David
D
Nairn
Rodney
R
D000818:Animals; D003532:Cyprinodontiformes / Q000235:genetics*; D004249:DNA Damage; D008546:Melanoma, Experimental / Q000209:etiology* / Q000473:pathology; D009381:Neoplasms, Radiation-Induced / Q000209:etiology* / Q000473:pathology; D012878:Skin Neoplasms / Q000209:etiology* / Q000473:pathology; D013472:Sunlight