Species and strain comparisons in the macromolecular binding of extremely low doses of [14C]benzene in rodents, using accelerator mass spectrometry.
The kinetics of macromolecular binding of a 5 micrograms/kg body wt dose of [14C]benzene was studied over 48 h in B6C3F1, DBA/2, and C57BL/6 mice and Fischer rats to determine if adduct levels reflect known differences in metabolic capacity, genotoxicity, and carcinogenic potency. Previous studies have suggested that differences in benzene toxicity among strains result from differences in metabolism. Rats and mice were administered [14C]benzene (i.p.), followed by removal of liver and bone marrow at time intervals up to 48 h postexposure. Protein and DNA were isolated and analyzed by accelerator mass spectrometry. Area under the curves for protein and DNA adducts in bone marrow were greatest in B6C3F1 mouse > DBA/2 mouse > C57BL/6 mouse > Fischer rat. These data are consistent with the hypothesis that metabolic capacity contributes to the difference in benzene's carcinogenicity among species. Additionally, these data suggest that target organ adduct levels correlate with tumorigenicity and thus may be indicative of an individuals risk.
Mani
C
C
Department of Pharmaceutical Chemistry, University of California, San Francisco 94143, USA.
Freeman
S
S
Nelson
D O
DO
Vogel
J S
JS
Turteltaub
K W
KW
D000818:Animals; D001554:Benzene / Q000378:metabolism*; D001853:Bone Marrow / Q000187:drug effects* / Q000378:metabolism*; D018736:DNA Adducts; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011485:Protein Binding / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D013045:Species Specificity; D013997:Time Factors
D018736:DNA Adducts; D001554:Benzene