Effect on topical 5-methoxypsoralen on tumorigenesis induced in albino and pigmented hairless mouse skin by UV irradiation.
A new line of the Skh:HRII hairless pigmented mouse (black juvenile coat) is described which has been selectively bred for the capacity to respond consistently to simulated solar UV radiation with a continuous and strong tan. This mouse demonstrates a degree of protection from chronic UV-induced tumorigenesis when compared with the Skh:HRI hairless albino mouse, and has been used here to study the effect of induced melanogenesis on phototumorigenesis. Mice were irradiated for 10 weeks with incremental doses of simulated solar UV radiation (UVA + B) from a fluorescent tube source which induced tumours in 100% of albino mice and 93% of black mice by 200 days (minimally oedemal), or with 60% of this dose (sub-oedemal) which induced tumours in 85% of albino mice and 65% of black mice. Mice were also exposed to the UVA component of these radiation sources, obtained by window glass filtration. The effect of topical 5-methoxypsoralen (5-MOP) was examined, at either 0.003% with minimally oedemal UVA + B or its UVA component alone, or at 0.01% with sub-oedemal UVA + B or its UVA component alone, in both albino and black mice. The 5-MOP concentrations were selected as the maximum concentration which did not increase the erythema and oedema responses after a single exposure to minimally oedemal or sub-oedemal UVA + B. At 200 days, the tumorigenic response to sub-oedemal UVA + B was significantly increased by topical 5-MOP, to 100% in albinos and 93% in black mice. In contrast, tumorigenesis in response to minimally oedemal UVA + B was unaffected by topical 5-MOP. The UVA component alone of either irradiation regime was not tumorigenic under these conditions. When combined with topical 5-MOP, the UVA of minimally oedemal UVA + B became moderately tumorigenic, and resulted in a tumour incidence of 23% in albinos and 14.5% in black mice. However, the UVA component of sub-oedemal UVA + B, when combined with topical 5-MOP, was highly tumorigenic specifically in albino mice, inducing tumours in 93% of albino mice but in only 27% of black mice. Tan intensity resulting from minimally oedemal UVA + B was not enhanced by topical 5-MOP, and its UVA component combined with 5-MOP resulted in only a minimal tan. However, the tan intensity resulting from sub-oedemal UVA + B with topical 5-MOP was strongly increased, although its UVA component combined with 5-MOP did not produce a perceptible tan.(ABSTRACT TRUNCATED AT 400 WORDS)
Reeve
V E
VE
Department of Veterinary Pathology, University of Sydney, N.S.W., Australia.
Greenoak
G E
GE
Boehm-Wilcox
C
C
Canfield
P J
PJ
Gallagher
C H
CH
D000078223:5-Methoxypsoralen; D000417:Albinism; D000818:Animals; D004307:Dose-Response Relationship, Radiation; D007536:Isomerism; D008730:Methoxsalen / Q000627:therapeutic use*; D051379:Mice; D008812:Mice, Hairless; D008817:Mice, Mutant Strains; D009381:Neoplasms, Radiation-Induced / Q000473:pathology / Q000517:prevention & control*; D010858:Pigmentation / Q000187:drug effects / Q000528:radiation effects; D012867:Skin / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D012878:Skin Neoplasms / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D014466:Ultraviolet Rays
D000078223:5-Methoxypsoralen; D008730:Methoxsalen