Retinol supplementation induces DNA damage and modulates iron turnover in rat Sertoli cells

Recent intervention studies revealed that supplementation with retinoids re sulted in a higher incidence of lung cancer. Recently the causal mechanism has begun to be clarified. We report here that retinol caused cellular DNA damage probably involving cellular iron accumulation. Retinol (7 muM) signi ficantly induced DNA single strands breaks, DNA fragmentation and productio n of 8-oxo-7, 8-dihydro-2'-deoxyguanosine in cultured Sertoli cells. In con trast, lower doses seemed not to induce single-strands break in this experi mental model. The breaks in DNA were inhibited by an iron scavenger; and 7 muM retinol treatment modulated iron turnover leading to iron accumulation, suggesting that iron ions were required for the retinol cellular effects. These findings suggest that retinol-induced DNA damage was associated with the modulation of iron turnover, and these characteristics could be respons ible for the increased incidence of lung cancer associated with retinoids s upplementation.