Decreased retinyl ester concentrations in UV-induced murine squamous cell carcinomas

Abstract

Squamous cell carcinomas were induced in hairless mice by repeated irradiations with UVB (280-320 nm, total dose 30 J/cm2) plus UVA (320-400 nm, total dose 168 J/cm2). The irradiated animals and non-irradiated controls were fed on diets with or without vitamin A supplementation (20,000 IU/kg). At the appearance of tumours, 30 to 43 weeks after the last irradiation, the vitamin A (retinol plus retinyl ester) concentrations in the serum, liver, epidermis and tumours and the retinol esterifying activities in microsomes from epidermis and tumours were measured. The liver and epidermal vitamin A concentrations were 2-3 times higher in vitamin A supplemented than in unsupplemented animals, but did not differ between tumour-bearing animals and non-irradiated controls receiving identical diets. The vitamin A concentration in the tumours was significantly lower than in perilesional epidermis. The largest difference (p less than 0.001) between the tumour and epidermal values was observed in the vitamin A supplemented group. The low vitamin A content of the tumours was entirely due to a marked (2 to 6-fold) reduction in the retinyl ester fraction. In contrast, the retinol content of the tumours was increased to twice that of normal epidermis. The activity of the esterifying enzyme, acyl-CoA:retinol acyltransferase (EC 2.3.1.76), was unchanged. The reason for the reduced retinyl ester concentration thus remains unclear. Still, it is possible that a disturbed interconversion of retinol to retinyl esters plays a role in murine photo-carcinogenesis.