Potentiating effect of dietary vitamin A on photocarcinogenesis in hairless mice.
Vitamin A and its derivatives (retinoids) exert modulatory effects on epithelial differentiation and are used therapeutically against skin cancers, but the role of dietary vitamin A in ultraviolet (UV)-induced carcinogenesis is far from clear. To study this process, 220 hairless mice were given diets containing low (0.3-0.6 mg/kg; A-) or high (4-6 mg/kg; A+) amounts of retinol, which resulted after 2 months in an approximately 4-fold difference in liver and skin vitamin A levels as determined by HPLC. Commencing after 1 month of diet, daily irradiations with UVB (280-320 nm) or UVAB (280-380 nm) were given to 176 of the animals for 18 weeks (cumulative doses of UVB and UVA: 26 J/cm2 and 168 J/cm2, respectively). The first skin tumours, known to be squamous cell carcinomas, appeared after 35 weeks in the UVAB-irradiated A+ animals and 5-6 weeks later in the other groups. After one year the frequency of tumour-bearing animals was 49-63% in the A+ groups and 28-39% in the A- groups (P = 0.003). Two months later the corresponding figures were 66-72% and 50-53%, respectively (P = 0.014). Disregarding the effect of dietary vitamin A, there was no difference in the final tumour incidence between UVB- and UVAB-irradiated animals. The epidermal vitamin A content at 72 h post-irradiation was approximately 60% lower in A+ animals and approximately 10% lower in A- animals compared with the non-irradiated controls. Rather than protecting against skin cancer, a diet rich in vitamin A seems to facilitate UV carcinogenesis in hairless mice. A possible explanation is that photodecomposition of excessive vitamin A generates short-lived intermediates that may act as photosensitizers during cutaneous carcinogenesis.
Mikkelsen
S
S
Department of Dermatology, The Finsen Institute, Copenhagen, Denmark.
Berne
B
B
Staberg
B
B
Vahlquist
A
A
D000818:Animals; D003043:Cocarcinogenesis; D004032:Diet; D051379:Mice; D008812:Mice, Hairless; D009381:Neoplasms, Radiation-Induced / Q000209:etiology*; D010865:Pilot Projects; D012867:Skin / Q000378:metabolism; D012878:Skin Neoplasms / Q000209:etiology*; D014801:Vitamin A / Q000008:administration & dosage* / Q000378:metabolism
D014801:Vitamin A