Cytosolic xanthine oxidoreductase mediated bioactivation of ethanol to acetaldehyde and free radicals in rat breast tissue. Its potential role in alcohol-promoted mammary cancer

Citation
Gd. Castro et al., Cytosolic xanthine oxidoreductase mediated bioactivation of ethanol to acetaldehyde and free radicals in rat breast tissue. Its potential role in alcohol-promoted mammary cancer, TOXICOLOGY, 160(1-3), 2001, pp. 11-18
Citations number
48
Categorie Soggetti
Pharmacology & Toxicology
Journal title
TOXICOLOGY
ISSN journal
0300483X → ACNP
Volume
160
Issue
1-3
Year of publication
2001
Pages
11 - 18
Database
ISI
SICI code
0300-483X(20010307)160:1-3<11:CXOMBO>2.0.ZU;2-H
Abstract
Epidemiological evidence links alcohol intake with increased risk in breast cancer. Not all the characteristics of the correlation can be explained in terms of changes in hormonal factors. In this work. we explore the possibi lity that alcohol were activated to acetaldehyde and free radicals in situ by xanthine dehydrogenase (XDh) and xanthine oxidase (XO) and/or aldehyde o xidase (AO). Incubation of cytosolic fraction with xanthine oxidoreductase (XDh + XO) (XOR) cosubstrates (e.g. NAD(+), hypoxanthine, xanthine, caffein e, theobromine, theophylline or 1,7-dimethylxanthine) significantly enhance d the biotransformation of ethanol to acetaldehyde. The process was inhibit ed by allopurinol and not by pyrazole or benzoate or desferrioxamine and wa s not accompanied by detectable formation of 1HEt. However, hydroxylated ar omatic derivatives of PEN were detected, suggesting either that hydroxyl fr ee radicals might be formed or that XOR might catalyze aromatic hydroxylati on of PEN. No bioactivation of ethanol to acetaldehyde was detectable when a cosubstrate of AO such as N-methylnicotinamide was included in cytosolic incubation mixtures. Results suggest that bioactivation of ethanol in situ to a carcinogen, such as acetaldehyde, and potentially to free radicals, mi ght be involved in alcohol breast cancer induction. This might be the case, particularly also in cases of a high consumption of purine-rich food (e.g. meat) or beverages or soft drinks containing caffeine. (C) 2001 Elsevier S cience Ireland Ltd. All rights reserved.