Ethanol-induced oxidative stress and acetaldehyde formation in rat mammary tissue: potential factors involved in alcohol drinking promotion of breast cancer.
Recent studies from our laboratory provided evidence that part of the carcinogenic effects of ethanol consumption might be related to its in situ metabolism at cytosolic and microsomal levels, to the mutagen acetaldehyde and to hydroxyl and 1-hydroxyethyl radicals. In this work, we report on our experiments where Sprague-Dawley female rats were exposed to the standard Lieber & De Carli diet for 28 days. We observed: the induction of the (xanthineoxidoreductase mediated) cytosolic and microsomal (lipoxygenase mediated) pathways of ethanol metabolism; promotion of oxidative stress as shown by increased formation of lipid hydroperoxides; delay in the t-butylhydroperoxide induced chemiluminiscence, and a significant decrease in protein sulfhydryls. In addition, the epithelial cells showed ultrastructural alterations consisting of markedly irregular nuclei, with frequent invaginations at the level of the nuclear envelope, condensation of chromatin around the inner nuclear membrane, and marked dilatation of the nuclear pores showing filamentous material exiting to the cytoplasm. In conclusion, the presence in mammary epithelial cells of cytosolic and microsomal pathways of ethanol bioactivation to carcinogenic and to tumorigenic metabolites might play a role in alcohol promotion of breast cancer.
Castro
Gerardo D
GD
Centro de Investigaciones Toxicológicas (CEITOX), CITEFA/CONICET, J.B. de La Salle 4397, B1603ALO Villa Martelli, Provincia de Buenos Aires, Argentina. gcastro@citefa.gov.ar
de Castro
Carmen Rodríguez
CR
Maciel
María E
ME
Fanelli
Silvia L
SL
de Ferreyra
Elida Cignoli
EC
Gómez
María I Díaz
MI
Castro
José A
JA
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000079:Acetaldehyde / Q000378:metabolism*; D000428:Alcohol Drinking / Q000009:adverse effects*; D000818:Animals; D001943:Breast Neoplasms / Q000139:chemically induced*; D002492:Central Nervous System Depressants / Q000378:metabolism / Q000633:toxicity*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004032:Diet; D000431:Ethanol / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D005456:Fluorescent Dyes / Q000633:toxicity; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010636:Phenols; D051381:Rats; D017207:Rats, Sprague-Dawley; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013454:Sulfoxides; D014969:Xanthine Oxidase / Q000378:metabolism; D014992:Xylenes / Q000633:toxicity
D002492:Central Nervous System Depressants; D005456:Fluorescent Dyes; D005609:Free Radicals; D010636:Phenols; D013438:Sulfhydryl Compounds; D013454:Sulfoxides; D014992:Xylenes; D000431:Ethanol; D000080242:8-Hydroxy-2'-Deoxyguanosine; D014969:Xanthine Oxidase; D003849:Deoxyguanosine; D000079:Acetaldehyde; C016833:xylenol orange