The augmentation of melanocytic nevi in guinea pigs by solar-simulated light: an animal model for human melanocytic nevi.
Strong epidemiological evidence confirms the role of sunlight in human melanoma induction. Furthermore, the frequency of melanocytic nevi is a good indicator of future development of melanoma and a short-term marker of adverse reactions to melanoma-inducing sun exposure in humans. Thus, the aim of this study was to develop and define an animal model for sunlight-induced nevi that can be used as a surrogate model for sunlight-induced melanoma. Five treatment groups of 30-40 Hartley albino guinea pigs/group were treated with topical 7,12-dimethylbenzanthracene at a dose range of 6-240 mg on the dorsum of the skin. At week 20, half of the animals in each group were given a 12-month regimen of minimal erythemal solar-simulated light, 3 times/week, increased weekly to maintain erythema. These regimes induced epidermally derived pigmented melanocytic nevi clinically and histologically similar to human nevi (junctional, compound, and dermal). S100 and HMB45 staining was also consistent with the patterns seen in human nevi. In contrast to the high-dose 7,12-dimethylbenzanthracene-treated animals (60 and 240 mg), where solar-simulated light had no effect on nevi multiplicity, those groups treated with low doses (24, 12, and 6 mg) had a significant increase in nevi multiplicity after 12 months of solar-simulated light treatment (24 mg, 0.5 nevi/animal unirradiated versus 1.4 nevi/animal irradiated, P = 0.03; 12 mg, 0.2 unirradiated versus 1.2 irradiated, P = 0.02; 6 mg, 0 unirradiated versus 1.9 irradiated, P = 0.008). UVB-induced minimal erythemal dose was unaltered after exposure to photoreactivating light, consistent with the observation of others that placental mammals lack the DNA photolyase responsible for strong photoreactivation seen in nonplacental mammals and lower metazoans. Thus, our guinea pig model has some of the essential elements required to be a robust animal model for human nevi and a surrogate model for melanoma. These nevi are augmented by solar-simulated light, are histologically similar, occupy the same level within the skin, have the same natural history as human nevi, and are produced in an animal lacking strong photoreactivation. These features are not found in any previously described small laboratory animal model.
Menzies
S
S
Sydney Melanoma Unit, University of Sydney, Royal Prince Alfred Hospital, Camperdown, NSW, Australia. scott@mel.rpa.cs.nsw.gov.au
Khalil
M
M
Crotty
K
K
Bonin
A
A
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D002471:Cell Transformation, Neoplastic / Q000528:radiation effects; D003043:Cocarcinogenesis; D004255:Deoxyribodipyrimidine Photo-Lyase / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D009508:Nevus, Pigmented / Q000139:chemically induced / Q000209:etiology* / Q000473:pathology; D013472:Sunlight / Q000009:adverse effects*
D002273:Carcinogens; D015127:9,10-Dimethyl-1,2-benzanthracene; D004255:Deoxyribodipyrimidine Photo-Lyase