Prevention of benzene-induced myelotoxicity by nonsteroidal anti-inflammatory drugs.
Benzene affects hematopoietic progenitor cells leading to bone marrow depression and genotoxic effects such as micronucleus formation. Progenitor cell proliferation and differentiation are inhibited by prostaglandins produced by macrophages. Administration of benzene to DBA/2 or C57BL/6 mice caused a dose-dependent bone marrow depression and a significant increase in marrow prostaglandin E level and both were prevented by the coadministration of indomethacin and other inhibitors of the cyclooxygenase component of prostaglandin H synthase. Levels of benzene that decreased bone marrow cellularity also caused genotoxic effects measured as increased micronucleated polychromatic erythrocytes in peripheral blood, which was also prevented by the coadministration of indomethacin. These results suggest a possible role for prostaglandin synthase in benzene myelotoxicity; a mechanism by which this might occur is presented.
Kalf
G F
GF
Department of Biochemistry and Molecular Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107.
Schlosser
M J
MJ
Renz
J F
JF
Pirozzi
S J
SJ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000378:metabolism; D001554:Benzene / Q000633:toxicity*; D001855:Bone Marrow Diseases / Q000139:chemically induced / Q000517:prevention & control*; D007213:Indomethacin / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D015162:Micronucleus Tests; D019800:Phenol; D010636:Phenols / Q000378:metabolism; D011458:Prostaglandins E / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001095:Arachidonic Acids; D010636:Phenols; D011458:Prostaglandins E; D019800:Phenol; D001554:Benzene; D007213:Indomethacin