Isolation and characterization of two benzene-derived hemoglobin adducts in vivo in rats.
The present study was aimed at the characterization of the major adducts formed by reaction of the metabolites of [14C]benzene with rat hemoglobin in vivo. Groups of 12-week-old male Fisher rats received i.p. injections of a single dose of 10 mmol/kg body weight or three equal daily subdoses of 3.3 mmol/kg body weight of [14C]benzene. High-performance liquid chromatographic analysis of strong acid hydrolysates of the [14C]benzene-modified globin indicated that the two major adducts in rats cochromatographed with synthetic S-(2,5-dihydroxyphenyl)cysteine and S-phenylcysteine. These adducts were converted to O,O'-S-tris-acetyl-3-thiol-hydroquinone and S-phenylthioacetate, which were then characterized by gas chromatography/mass spectrometry. The major radioactive adduct peaks accounted for 60-75% of the total radioactivity associated with rat globin. Characterization of the S-(2,5-dihydroxyphenyl)cysteine adduct provides evidence that p-benzoquinone is formed as a reactive metabolite of benzene. Formation of the S-phenylcysteine adduct indicates that benzene oxide and/or a hydroxycyclohexadienyl free radical is formed as an active intermediate upon i.p. injection of benzene into rats.
Melikian
A A
AA
American Health Foundation, Naylor Dana Institute for Disease Prevention, Valhalla, New York 10595.
Prahalad
A K
AK
Coleman
S
S
D000818:Animals; D001554:Benzene / Q000008:administration & dosage / Q000302:isolation & purification* / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000302:isolation & purification; D008401:Gas Chromatography-Mass Spectrometry; D006454:Hemoglobins / Q000302:isolation & purification* / Q000378:metabolism*; D006868:Hydrolysis; D007274:Injections, Intraperitoneal; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
D002250:Carbon Radioisotopes; D006454:Hemoglobins; C042216:beta-phenylcysteine; C040165:2-(S-cysteinyl)hydroquinone; D001554:Benzene; D003545:Cysteine