The Monodelphis Melanoma Model: Initial Report on Large Ultraviolet A Exposures of Suckling Young

Abstract

The objective of this study was to determine whether exposure of early suckling young of the opossum Monodelphis domestica to ultraviolet A (UVA) radiation (320–400 nm) can lead to the development of melanocytic lesions similar to those induced after exposure to ultraviolet B (UVB) radiation (280–320 nm) to total doses as low as 380 J/m2. A total of 576 sucklings received nine exposures of 0.6, 2.6 or 15.5 kJ/m2 per dose (total doses ∼ 6, 23 and 140 kJ/m2 respectively) from a Blak Ray lamp source with a narrow range emission at 365 nm. A further 280 sucklings were exposed in the same way to doses of 2.6 kJ/m2 per dose (total ∼ 23 kJ/m2) broad‐band UVA with visible wavelengths from a Dermalight lamp. Frequency of litter loss following all of the UVA‐exposure protocols was similar to that within the same stocks in the colony at large. Only one of the 856 UVA‐exposed individuals possessed a melanocytic lesion at the 5 month assessment point. No radiation‐induced lesions of any type were evident on the skin of the other animals exposed as sucklings. The affected male was from a group of 70 individuals exposed to the highest total dose (140 kJ/m2) from the Blak Ray light source. The melanocytic hyperplasia was provisionally identified as a potential melanoma but it slowly regressed as the animal aged. We conclude that in the opossum suckling exposure system, the potency of UVA for melanoma induction is extremely low compared with that of UVB. Possible explanations, amenable to further investigations, are given for the low UVA sensitivity of the suckling model compared to the adult exposure model of Ley (Ley, R. D. [1997] Cancer Res.57, 3682–3684).

Ultraviolet A does not induce melanomas in a Xiphophorus hybrid fish model

“…UVB induces CMM in HGF/SF (5), HRAS/p19(ARF) +/− (20), and CDK4/HRAS mice (21). UVA does not induce melanomas in the albino HGF/SF mouse (5) or in the opossum (7). Consistent with these mammalian models we show that UVA does not induce melanomas in a backcross hybrid fish model.…”

“…Studies in mammalian models, including the South American opossum (Monodelphis domestica) and several genetically modified mouse models, demonstrate that UVA does not induce melanomas (5)(6)(7). In contrast, evidence from all of these models, including Xiphophorus, supports a role for UVB in the etiology of melanoma.…”

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“…However this could not be confirmed in later experiments (Mitchell et al, 2010). A mammalian opossum model also developed melanoma-like lesions after broadband UVA exposure but with low potency compared to broad-band UVB (Robinson et al, 2000).…”

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“…Studies in these fish however showed that visible and UVA radiation, as well as UVB (Setlow et al, 1993) induced lesions that raised concern that UVA might be causal for human melanoma as well or instead of UVB. A mammalian opossum model also developed SCCP/0949/05 Opinion on Biological effects of ultraviolet radiation relevant to health with particular reference to sun beds for cosmetic purposes melanoma-like lesions after broad-band UVA exposure but with low potency compared to broad-band UVB (Robinson et al, 2000). A mouse model was described in 2003 (the hepatocyte growth factors/scatter factor transgenic mouse) in which melanomas with a strong epidermal component were induced (Nonnan et al, 2003).…”