A proposed mechanism of benzene toxicity: Formation of reactive intermediates from polyphenol metabolites

Semiquinone anion radicals formed by the reaction of quinones with glutathione or amino acids

“…The biological importance of such reactions remains to be assessed and will depend on several factors including the intracellular concentrations of quinone, availability of thiol and other nucleophilic groups, and the one and two electron reductive metabolism of the quinone. Thus the bone marrow toxicity of benzene and phenol, which is believed to be mediated by a metabolite of phenol such as BQ [26], may in part be due to reactions similar to those described in the current study.…”

Pharmacokinetics and Metabolism of Benzene in Zymbal Gland and Other Key Target Tissues after Oral Administration in Rats

“…However, there was no indication that C was selectively retained by the Zymbal gland in comparison to mammary gland and adipose tissue. Since it has been reported that fatty tissues (e.g., adipose, bone marrow) might function as a depot or sink for benzene (9,27), one experiment was carried out to specifically deternine if 14C-benzene residues accumulate in the Zymbal gland (a sebaceous gland) after repeated oral exposure. After 2 weeks of oral dosing at 500 mg/kg (single dose daily 5 days per week for two weeks), no apparent accumulation of 14C was observed in the Zymbal gland compared to that after a single oral dose (data not shown).…”

“…Although the exact chemical nature of the ultimate toxic or carcinogenic species remains unknown, several metabolic pathways proposed for benzene lead to the formation of reactive intermediates. Of importance are those pathways giving rise to mono-and polyhydroxylated metabolites (e.g., phenol, hydroquinone, catechol, 1,2,4-benzenetriol), ring-opened metabolites (e.g., muconaldehyde, muconic acid) and biphenolic metabolites (e.g., 4,4'-biphenol) (9)(10)(11)(12)(13)(14)(15). The metabolism of benzene has been extensively studied in the liver and bone marrow (4,(19)(20)(21), but little effort has been than 99%.…”

Semiquinone Anion Radicals of Catechol(amine)s, Catechol Estrogens, and Their Metal Ion Complexes

“…Several xenobiotics (benzene, 4-bromobenzene, and acetominophen) undergo aromatic hydroxylation by cytochrome P-450 in the liver to form the corresponding catechol(s) (37)(38)(39)(40). In addition the hematopoietic toxicity ofbenzene and the nephrotoxicity ofbromobenzene has been linked to semiquinone/quinone production from catechol metabolites (37,38).…”

“…In addition the hematopoietic toxicity ofbenzene and the nephrotoxicity ofbromobenzene has been linked to semiquinone/quinone production from catechol metabolites (37,38).…”