Abstract
Cumulative lifetime ultraviolet radiation (UVR) is an important factor in the development of squamous cell carcinoma. This study examines the impact of UVR exposure pattern on tumor development. Hairless C3.Cg/TifBomTac immunocompetent pigmented mice (n = 351) were irradiated with 12 standard erythema doses (SED)/week, given as 2 SED ×6, 3 SED ×4, 4 SED ×3, or 6 SED ×2 (dose–delivery study) or 0, 0.6, 1.2, 2, 3 or 4 SED ×3/week (dose–response study). All mice were irradiated until development of 3 tumors of 4 mm each. Pigmentation was measured once monthly. In the dose–delivery study, the median time until tumor development was independent of dose fractions. In the dose–response study, higher UVR doses resulted in faster tumor appearance. When the weekly UVR dose was decreased from 12 to 6 SED, the cumulative UVR dose needed for tumor development was reduced by 40%. In conclusion, delivery schedules of a fixed weekly UVR dose did not affect tumor development. When using different weekly UVR doses, longer time to tumor development was observed using lower UVR doses. Lower weekly UVR doses however resulted in lower cumulative UVR doses to induce tumors in hairless pigmented mice.
Highlights
Sunlight is the most important carcinogen for non-melanoma skin cancer, and especially squamous cell carcinomas (SCC), due to the cumulative effect of long-term ultraviolet radiation (UVR) in both humans and mice [1,2]
This study investigated the carcinogenic effect of a few high UVR exposures compared with multiple smaller exposures
UVR exposure pattern was of no importance for tumor development using the same weekly UVR doses in the dose–delivery study
Summary
Sunlight is the most important carcinogen for non-melanoma skin cancer, and especially squamous cell carcinomas (SCC), due to the cumulative effect of long-term ultraviolet radiation (UVR) in both humans and mice [1,2]. UVR exposure pattern differs among e.g., rural and urban children [3,4], occupations and outdoor sports activities [4]. It is often discussed whether the cumulative UVR represents the only health and safety parameter of importance for the development of keratinocyte cancers in humans, as well as whether the pattern of UVR exposure matters [5]. Studies of the importance of UVR exposure patterns on skin cancer in mice have mainly been conducted on hairless albino mice [7,8,9], and, in some cases, on mice able to develop pigmentation [10,11]. Some studies show no or very little protection of induction of
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