The effect of acute and chronic exposure to acetaldehyde—a mutagenic metabolite of dietary ethanol—on prostate cancer cells: A potential source of race disparity disfavoring black men.

Abstract

143 Background: We recently reported that the ADH1B*3 allele, which is specific to African Americans (AA), when combined with ethanol intake may constitute a gene-environment interaction leading to elevated prostate cancer (CaP) and potentially aggressive CaP risk among AA men possibly through intra-prostatic acetaldehyde accumulation. Indeed, studies have shown microsomes from rat ventral prostates biotransform ethanol to acetaldehyde that further metabolizes into oxidative stress-inducing acetyl radicals. In addition, acetaldehyde has been previously shown to enhance proliferation of colon cancer cells. Whether acetaldehyde has the same effect on CaP is unknown. Methods: We subjected DU-145 CaP cells to varying concentrations of acetaldehyde using acute and chronic models of exposure and measured tumor proliferation using MTS assay. Proliferation was measured over 4 days of acetaldehyde treatment in acute and after 2 weeks of treatment in chronic exposure experiments. All experiments were conducted in triplicate. Results were expressed as mean values for each treatment referenced to untreated cells. Doubling times were calculated using least squares fitting exponential regression. Results: In the acute exposure model, proliferation of DU-145 cells was inhibited by 150 uM acetaldehyde by 28% while 1,500uM and higher concentrations resulted in complete inhibition of proliferation. After chronic exposure to acetaldehyde, proliferation of DU-145 cells was inhibited by 500 uM acetaldehyde by 19%. In contrast, chronic exposure with 1,000 uM acetaldehyde resulted in increased proliferation by 9% and shortened tumor doubling time. Conclusions: Acute exposure to acetaldehyde resulted in inhibition of CaP cellular proliferation. Chronic exposure to high acetaldehyde concentrations promoted tumor proliferation likely through selection for more robust CaP cells that survive the repeated chemical insult. Our results suggest that chronic acetaldehyde exposure of existent CaP may potentially promote disease aggressiveness. Uncovering mechanisms for enhanced CaP cell proliferation by acetaldehyde are warranted.