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