Structure-activity relationships in the induction of DNA-protein cross-links by hematotoxic ring-opened benzene metabolites and related compounds in HL60 cells.

摘要: Abstract Previous studies from our laboratory have demonstrated the formation of DNA–protein cross-links (DNAPC), a potentially cytotoxic and genotoxic lesion induced by many leukemogenic agents, in bone marrow cells mice administered benzene, however, reactive benzene metabolites involved DNAPC not been characterized. The present examined DNA PC HL60 treated with trans,trans-muconaldehyde (MUC), hematotoxic ring-opened metabolite as well MUC structurally related compounds. Using K+/SDS precipitation assay for determination, concentration- time-dependent increases were observed 2 4 h after treatment 50, 75 100 μM MUC. No levels measured 6-hydroxy-trans,trans-2,4-hexadienal (HOMCHO), 6-oxo-trans,trans-2,4-hexadienoic acid (CHOMCOOH), or trans,trans-muconic (HOOCMCOOH), each at μM. Significant 500 1000 HOMCHO, but CHOMCOOH. effect on was trans,trans-2,4-hexadienal, trans-2-hexenal, hexanal, trans,trans-2,4-hexadiene, glutaraldehyde, acrolein. HOMCHO may be lesions, these compounds correlated decreases cell viability. Except acrolein, inducing also did affect These suggest that both aldehydic carbons contribute to induction, presence α,β-unsaturated double bonds conjugated aldehyde groups ability induce relative saturated dialdehyde glutaraldehyde.