An experimental population study of nucleotide excision repair as a risk factor for UVB-induced melanoma

Abstract

Nucleotide excision repair (NER) is the primary defense against the DNA damage implicit in skin cancer formation and is negatively affected by chronic exposure to UVB radiation. However, in situ and in vitro studies consistently yield equivocal results when addressing individual DNA repair capacity and melanoma susceptibility. The primary objective of this study was to determine if individual global NER capacity is a risk factor for melanoma formation in a prominent UVB-inducible melanoma model, hybrid Xiphophorus fishes. After neonatal UVB irradiation, adult tumor-bearing and tumor-free fish were given a challenge UVB dose and (6-4) photoproduct repair was quantified in individual fish at 24 h using radioimmunoassay. Despite considerable inter-individual variation in repair capacity, ranging from 13% to 91%, we found no difference in mean NER capacity between fish with and without melanomas, thus detaching global NER from melanomagenesis. Furthermore, despite epidemiological data indicating that sex and age are important risk factors underlying melanoma susceptibility, we found no difference in mean NER rates among the sexes or as a function of age. We conclude with a discussion of the apparent paradox of how inter-individual variation in NER is not a risk factor given the clear evidence that DNA damage underlies melanoma susceptibility.

Figure 1

(6-4)PD excision capacity percentiles for the control (A) and neonatal UVB irradiated BC₁ fish (B). There was considerable inter-individual variation in (6-4)PD removal in a 24 hour period, however, the degree of variation was not significantly different between the control and neonatal UVB irradiated groups [F(1,136) = 1.445, P = 0.144). It is noteworthy that a portion of the melanomas in the UVB irradiated group (B) are likely spontaneous melanomas (i.e., not induced via UVB irradiation), which would contribute to the similarity in the variances of the two data sets.

Figure 1

(6-4)PD excision capacity percentiles for the control (A) and neonatal UVB irradiated BC₁ fish (B). There was considerable inter-individual variation in (6-4)PD removal in a 24 hour period, however, the degree of variation was not significantly different between the control and neonatal UVB irradiated groups [F(1,136) = 1.445, P = 0.144). It is noteworthy that a portion of the melanomas in the UVB irradiated group (B) are likely spontaneous melanomas (i.e., not induced via UVB irradiation), which would contribute to the similarity in the variances of the two data sets.