Artículo
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
Castro, Gerardo Daniel
; Delgado de Layño, Aurora M. A.; Costantini, Martin Hernan; Castro, Jose Alberto
Fecha de publicación:
12/2003
Editorial:
Wiley
Revista:
Teratogenesis Carcinogenesis And Mutagenesis
ISSN:
0270-3211
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
We recently showed that mammary cytosolic xanthineoxidoreductase had the ability to bioactivate ethanol (EtOH) to acetaldehyde (AC) and free radicals. In thepresent study, we report that the microsomal fraction also biotransforms EtOH to AC. One pathway requires NADPH and the others do not. Both need oxygen. TheNADPH-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 bydiethyldithiocarbamate (DDTC), sodium azide, and diphenyleneiodonium (DPI) butnot by desferrioxamine, which suggests a possible role of a non-ironcopper-requiring flavoenzyme. The process was partially inhibited bythiobenzamide (TBA), methylmercaptoimidazole (MMI), and nordihydroguaiaretic acid(NDG) but not by dapsone, aminotriazole, or indomethacin. These results suggestthe potential participation of flavine monooxygenase and of lipooxygenase or ofperoxidases/oxidases having similar characteristics but not of lactoperoxidase orcyclooxygenase. The pathway not requiring NADPH could also be partially inhibitedby DDTC, NDG, azide, DPI, and TBA or MMI but not by the other chemicals. Littleactivity proceeds under nitrogen. Oxidases or peroxidases might be involved. Noformation of 1-hydroxyethyl radicals was detected either in the presence orabsence of NADPH. The nature of the EtOH bioactivating enzymes involved remainsto be established. However, the fact remains that an activation of EtOH to AC wasfound in mammary tissue and could have a significant effect in some stages of theprocess of breast tumor promotion by EtOH.
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Articulos(UNIDEF)
Articulos de UNIDAD DE INVESTIGACION Y DESARROLLO ESTRATEGICOS PARA LA DEFENSA
Articulos de UNIDAD DE INVESTIGACION Y DESARROLLO ESTRATEGICOS PARA LA DEFENSA
Citación
Castro, Gerardo Daniel; Delgado de Layño, Aurora M. A.; Costantini, Martin Hernan; Castro, Jose Alberto; 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; Wiley; Teratogenesis Carcinogenesis And Mutagenesis; 23; S1; 12-2003; 61-70
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