The hematotoxic effects of 6-hydroxy-trans,trans-2,4-hexadienal, a reactive metabolite of trans,trans-muconaldehyde, in CD-1 mice.
6-Hydroxy-trans,trans-2,4-hexadienal (CHO-M-OH) is a metabolite of trans,trans-muconaldehyde (muconaldehyde or MUC), a microsomal hematotoxic ring-opened metabolite of benzene. In the present study, the toxicity of CHO-M-OH was examined. In order to assess potential toxic effects of CHO-M-OH on the maturation of erythroid cells in the bone marrow, 10-week-old male CD-1 mice were administered CHO-M-OH intraperitoneally and 59Fe incorporation into erythrocytes was measured. The uptake of 59Fe by erythroid cells was significantly inhibited at doses of 20, 25, and 30 mg/kg. There was no inhibition of 59Fe incorporation at a dose of 15 mg/kg. In other hematotoxicity studies, bone marrow cellularity, peripheral blood cells, and sulfhydryl contents in bone marrow cells were examined in mice administered CHO-M-OH intraperitoneally. An increase in the white blood cell count was observed in mice treated with 5 mg/kg/day for 16 consecutive days, while bone marrow cellularity and red blood cell parameters were not changed. Administration of 10 mg/kg/day for 16 consecutive days caused a significant decrease in sulfhydryls of bone marrow cells but no changes in bone marrow cellularity and peripheral blood parameters compared with controls. At a dose of 25 mg/kg/day for 4 days, there was a significant decrease in nucleated bone marrow cells. The white blood cell count, mainly lymphocytes, also significantly decreased. Our results indicate that CHO-M-OH is a hematotoxin in mice and conceivably could play a role in benzene toxicity.
Zhang
Z
Z
Joint Graduate Program in Toxicology, Rutgers University/UMDNJ-Robert Wood Johnson Medical School, Piscataway, USA.
Schafer
F
F
Schoenfeld
H
H
Cooper
K
K
Snyder
R
R
Goldstein
B D
BD
Witz
G
G
D000447:Aldehydes / Q000378:metabolism / Q000633:toxicity*; D000466:Alkadienes / Q000633:toxicity*; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D006402:Hematologic Diseases / Q000139:chemically induced*; D007501:Iron / Q000378:metabolism; D007504:Iron Radioisotopes; D008297:Male; D051379:Mice
D000447:Aldehydes; D000466:Alkadienes; D007504:Iron Radioisotopes; C083262:6-hydroxyhexa-2,4-dienal; C034476:muconaldehyde; D007501:Iron