No abstract

Mice were given either β-carotene or either of two carotenoids with no vitamin A activity – canthaxanthin or phytoene – or placebo. Skin tumors were induced in each group by each of three methods: (1) UV-B (290–320 nm); (2) dimethylbenz(a)anthracene (DMBA)/croton oil applications; (3) DMBA followed by low-dose UV-B. For tumors induced by UV-B alone, β-carotene-phytoene- and canthaxanthin-treated mice developed fewer tumors per mouse, with a delay in tumor appearance, than did control mice. For tumors induced by DMBA/croton oil or DMBA/UV-B, mice receiving β-carotene showed a significant difference in tumor numbers and appearance time from placebo mice; phytoene and canthaxanthin treatment had no effect.

Definitive cure of an animal model of a human disease by gene transfer into hematopoietic stem cells has not yet been accomplished in the absence of spontaneous in vivo selection for transduced cells. Erythropoietic protoporphyria is a genetic disease in which ferrochelatase is defective. Protoporphyrin accumulates in erythrocytes, leaks into the plasma and results in severe skin photosensitivity. Using a mouse model of erythropoietic protoporphyria, we demonstrate here that ex vivo preselection of hematopoietic stem cells transduced with a polycistronic retrovirus expressing both human ferrochelatase and green fluorescent protein results in complete and long-term correction of skin photosensitivity in all transplanted mice.

Studies in bacteria, animals and humans have demonstrated that carotenoid pigments can prevent or lessen photosensitivity by endogenous photosensitizers such as chlorophyll or porphyrins, as well as by exogenous photosensitizers such as dyes (e.g., toluidine blue) or porphyrin derivatives. The carotenoids beta-carotene and canthaxanthin have been found to be effective in the treatment of the photosensitivity associated with EPP and certain other photosensitivity diseases. No serious toxicity has been reported from their use, although the use of canthaxanthin is not recommended because of its propensity to form retinal granules. The pigments perform their protective function by quenching excited species formed by the interaction of porphyrins or dyes, light and air, thereby preventing the cellular damage which leads to the symptoms of photosensitivity.