Induction of nevi and skin tumors in Ink4a/Arf Xpa knockout mice by neonatal, intermittent, or chronic UVB exposures.

Nevi and melanomas correlate to childhood and intermittent solar UV exposure, xeroderma pigmentosum patients run increased risk, and p16(Ink4a) expression is often lost in malignant progression. To ascertain the effect of these risk factors, pigmented hairless Ink4a/Arf-, Xpa- knockout mice were subjected to various combinations of neonatal [7,12-dimethylbenz(a)anthracene (DMBA) or UVB exposure] and adult treatments (12-O-tetradecanoylphorbol-13-acetate or subacute daily UVB exposure or intermittent overexposure). Nevi occurred earliest, grew largest, and were most numerous in mice exposed to DMBA followed by intermittent UVB overexposure [effect of six minimal edemal doses (MED), 1 x /2 weeks > 4 MED 1 x /wk].

Single UVB overexposure stimulates melanocyte proliferation in murine skin, in contrast to fractionated or UVA-1 exposure.

Overexposure to short- and long-wave ultraviolet radiations (UVB, UVA) may contribute to melanoma development through combined genotoxic and mitogenic effects in melanocytes. This study compares the impact of UVA-1 versus UVB, and single versus fractionated exposures on melanocyte proliferation in hairless SKH-2 mice. A single erythemal dose was compared with an equal dose fractionated over 8 d, and dose-dependency was studied.