Rat breast microsomal biotransformation of ethanol to acetaldehyde but not to free radicals: its potential role in the association between alcohol drinking and breast tumor promotion.
We recently showed that mammary cytosolic xanthineoxidoreductase had the ability to bioactivate ethanol (EtOH) to acetaldehyde (AC) and free radicals. In the present study, we report that the microsomal fraction also biotransforms EtOH to AC. One pathway requires NADPH and the others do not. Both need oxygen. The NADPH-dependent pathway is not inhibited by CO:O(2) (80:20) or SKF 525A and that excludes the participation of cytochrome P450. It is inhibited by diethyldithiocarbamate (DDTC), sodium azide, and diphenyleneiodonium (DPI) but not by desferrioxamine, which suggests a possible role of a non-iron copper-requiring flavoenzyme. The process was partially inhibited by thiobenzamide (TBA), methylmercaptoimidazole (MMI), and nordihydroguaiaretic acid (NDG) but not by dapsone, aminotriazole, or indomethacin. These results suggest the potential participation of flavine monooxygenase and of lipooxygenase or of peroxidases/oxidases having similar characteristics but not of lactoperoxidase or cyclooxygenase. The pathway not requiring NADPH could also be partially inhibited by DDTC, NDG, azide, DPI, and TBA or MMI but not by the other chemicals. Little activity proceeds under nitrogen. Oxidases or peroxidases might be involved. No formation of 1-hydroxyethyl radicals was detected either in the presence or absence of NADPH. The nature of the EtOH bioactivating enzymes involved remains to be established. However, the fact remains that an activation of EtOH to AC was found in mammary tissue and could have a significant effect in some stages of the process of breast tumor promotion by EtOH.
Castro
G D
GD
Centro de Investigaciones Toxicológicas (CEITOX)-CITEFA/CONICET, Buenos Aires, Argentina.
Delgado de Layño
A M A
AM
Costantini
M H
MH
Castro
J A
JA
D000079:Acetaldehyde / Q000378:metabolism*; D000428:Alcohol Drinking / Q000009:adverse effects*; D000818:Animals; D001711:Biotransformation; D000431:Ethanol / Q000302:isolation & purification / Q000378:metabolism*; D005260:Female; D005609:Free Radicals / Q000378:metabolism*; D008321:Mammary Glands, Animal / Q000378:metabolism*; D015674:Mammary Neoplasms, Animal / Q000209:etiology* / Q000378:metabolism*; D008861:Microsomes / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005609:Free Radicals; C065424:1-hydroxyethyl radical; D000431:Ethanol; D000079:Acetaldehyde