Premium
Phenol/Hydroquinone Reduces Lymphocyte Counts and Produces Quinol‐Thioether‐ and 4‐Hydroxy‐2‐nonenal‐ Modified Proteins: Implications for Benzene‐Mediated Hematotoxicity
Author(s) -
Kuhlman Christopher Lee,
Petersen Dennis R.,
Monks Terrence J.,
Lau Serrine S.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.620.13
Benzene exposure causes myelotoxicity and leukemia. Phenol and hydroquinone (PHE/HQ; 1.1/0.9 mmol/kg, ip, 19h), metabolites of benzene, significantly decrease lymphocyte counts (58–89%) in rats. HQ readily oxidizes to 1,4‐BQ and conjugates with GSH, and multi‐substituted HQ‐GSHs were detected in bone marrow after PHE/HQ. HQ‐GSH conjugates retain the ability to arylate proteins and to redox cycle, HQ‐GSHs being more efficient generators of superoxide anion than HQ/1,4‐BQ. However, the precise molecular mechanism(s) by which benzene/HQ‐GSH conjugates induce hematotoxicity is unknown. Using anti‐(GS/NACys)HQ and anti‐4‐hydroxy‐2‐nonenal (4HNE) specific antibodies on 1D/2D western, and MS/MS peptide sequencing analysis of immunopositive proteins from bone marrow lysate of rats treated with PHE/HQ, revealed the presence of 35 (GS/NACys)HQ‐ and 4HNE‐adducted proteins. Moreover, HQ‐GSH (E, K, R) and 4HNE (C, H, K) adduction sites were identified on 10 proteins. HQ‐GSH adducted hemoglobin‐α,β (Hb), ribose 5‐phosphate isomerase A (RPI), β‐,α‐enolase, annexin A‐1, tropomyosin‐α4 and nonO/p54nrb while 4HNE modified Hb, RPI, carbonic anhydrase 1, and bisphosphoglycerate mutase. Analysis of the structural and functional significance of these protein modifications may provide new insight into the progression of benzene‐induced leukemia. (P30ES006694, RO1GM70890, Sci. Found. of AZ, T32ES007091)