Further studies on the contribution of acetaldehyde accumulation in rat mammary

S.L. FANELLI; M. E. MACIEL; M.I. DÍAZ GÓMEZ; F. BIETTO; J.A. CASTRO; G.D. CASTRO

Helsinski

Congreso; The 12th Congress of European Society fo Biomedical Research on Alcoholism; 2009

University of Helsinki and the Finnish Society of Addiction

There is available evidence supporting a positive association between alcohol intake and risk of breast cancer. However, there is limited information regarding possible mechanisms for this effect. Past  studies from our laboratory suggest that  accumulation acetaldehyde in mammary tissue after alcohol intake may be of particular relevance and that cytosolic and microsomal in situ bioactivation of ethanol to acetaldehyde and free radicals and the resulting oxidative stress promotion could be a significant event related to tumour promotion. In this work we report further studies concerning these hypothesis. Sprague Dawley rats received a Lieber De Carli standard diet for 28 days. Controls were pair fed. Animals were sacrificed and processed for different determinations like GSH content; GSSG reductase; GSHPx and alpha-tocopherol. Further attempts to characterize the microsomal activation step via inhibition studies and chlorzoxazone hydroxylase and lipoxygenase were made. Additional tests for lipid peroxidation detection were also made: UV diene conjugation and MDA production by HPLC. Comparison against equivalent results in liver was made. Other additional tests included comet assay; immunohistochemical studies for p53 expression and apoptosis. Obtained results showed significant decreases in GSH; GST; GSSG-reductase and alpha-tocopherol; GSHPx was slightly increased. UV diene conjugation and MDA determinations did not evidence lipid peroxidation occurrence while xylenol orange procedure gave positive results. Mammary microsomal metabolism of ethanol to acetaldehyde was not induced after an acute dose of ethanol able to induce the liver counterpart. Acetone, another inducer of CYP2E1 in liver, also failed to induce the microsomal ethanol metabolizing pathway. No increased generation of comet images or in p53 expression were found in either mammary tissue or in liver under the experimental conditions tested. Results suggest that while acetaldehyde accumulation in mammary tissue could be critical event resulting from increasing  production of acetaldehyde in situ plus additional amount arriving via blood, other factors such as poor handling of the accumulated acetaldehyde via different defences could be also relevant. There remains to be further characterized the microsomal activation system while the cytosolic one has been  reasonably well established as being xanthine oxidoreductase. Supported by ANPCyT (PICT 25354) and CONICET (PIP 5158).