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Titolo:
REACTIVE RING-OPENED ALDEHYDE METABOLITES IN BENZENE HEMATOTOXICITY
Autore:
WITZ G; ZHANG ZH; GOLDSTEIN BD;
Indirizzi:
UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,ENVIRONM & OCCUPAT HLTH SCI INST PISCATAWAY NJ 08855
Titolo Testata:
Environmental health perspectives
, volume: 104, anno: 1996, supplemento:, 6
pagine: 1195 - 1199
SICI:
0091-6765(1996)104:<1195:RRAMIB>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
ANION RADICAL PRODUCTION; TRANS,TRANS-MUCONIC ACID; POTENTIAL ROLE; LIVER; TOXICITY; CELLS; IDENTIFICATION; MUCONALDEHYDE; PEROXIDASE; INHIBITION;
Keywords:
TRANS-TRANS-MUCONALDEHYDE; RING-OPENED BENZENE METABOLITES; BENZENE; METABOLISM;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
37
Recensione:
Indirizzi per estratti:
Citazione:
G. Witz et al., "REACTIVE RING-OPENED ALDEHYDE METABOLITES IN BENZENE HEMATOTOXICITY", Environmental health perspectives, 104, 1996, pp. 1195-1199

Abstract

The hematotoxicity of benzene is mediated by reactive benzene metabolites and possibly by other intermediates including reactive oxygen species. We previously hypothesized that ring-opened metabolites may significantly contribute to benzene hematotoxicity. Consistent with this hypothesis, our studies initially demonstrated that benzene is metabolized in vitro to trans-trans-muconaldehyde (MUC); a reactive six-carbondiene dialdehyde, and that MUC is toxic to the bone marrow in a manner similar to benzene. Benzene toxicity most likely involves interactions among several metabolites that operate by different mechanisms to produce more than one biological effect. Our studies indicate that MUC coadministered with hydroquinone is a particularly potent metabolite combination that causes bane marrow damage, suggesting that the involvement of ring-opened metabolites in benzene toxicity may be related to their biological effects in combination with other benzene metabolites. Studies in our laboratory and by others indicate that MUC is metabolized to a variety of compounds by oxidation or reduction of the aldehyde groups. The aldehydic MUC metabolite 6-hydroxy-trans-trans-2,4-hexadienal (CHO-M-OH), similar to MUC but to a lesser extent, is reactive toward glutathione, mutagenic in V79 cells, and hematotoxic in mice. It is formed by monoreduction of MUG, a process that is reversible and could be of biological significance in benzene bone marrow toxicity. The MUC metabolite 6-hydroxy-trans-trans-2,4-hexadienoic (COOH-M-OH) isan end product of MUC metabolism in vitro. Our studies indicate that COOH-M-OH is a urinary metabolite of benzene in mice, a finding that provides further indirect evidence for the in vivo formation of MUC from benzene. Mechanistic studies showed the formation of cis-trans-muconaldehyde in addition to MUC from benzene incubated in a hydroxyl radical-generating Fenton system. These results suggest that the benzene ring is initially opened to cis,cis-muconaldehyde, an unstable isomer that rearranges to cis-trans-muconaldehyde, which further rearranges to trans-trans-muconaldehyde. The latter is not formed from benzene dihydrodiol by reactive oxygen species in a Fenton system that contains reactive oxygen species.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/09/20 alle ore 10:57:24