Binding of chloroform to mouse and rat hemoglobin.
The covalent binding of chemical carcinogens and mutagens to hemoglobin has been proposed as a dose monitor for environmental exposure. The binding of chloroform to hemoglobin in rats was demonstrated to result from the formation of addition adducts to amino acids in the globin. The altered amino acids were isolated with an amino acid analyzer employing ion exchange chromatography. The covalent binding of orally-administered [14C]chloroform to rat hemoglobin reached a peak within 10 h. Afterwards, the amount of chloroform bound decreased slowly with half remaining at 7 weeks. The extent of chloroform binding was linearly dependent upon dose between 0.1 and 100 mumol/kg. Above 100 mumol/kg chloroform the binding to hemoglobin increased at a reduced rate. The extent of [14C]chloroform binding resulting from either 10 daily doses of 0.1 mumol/kg or a single 1.0 mumol/kg was similar. The binding to hemoglobin in three strains of mice and rats varied from 85 +/- 7 mumol/g Hb for Swiss (CFN) mice to 152 +/- 14 for Fisher-344 rats. We have demonstrated that the binding of chloroform to hemoglobin appears to have the following attributes of a dose monitor: (1) easily accessible from laboratory animals (and humans); (2) dose dependent; (3) stability, so that exposure can be determined weeks after it has ceased; (4) integration of low exposures which individually would be undetectable.
D000596:Amino Acids / Q000302:isolation & purification; D000818:Animals; D002725:Chloroform / Q000097:blood*; D006454:Hemoglobins / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011485:Protein Binding; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013997:Time Factors
D000596:Amino Acids; D006454:Hemoglobins; D002725:Chloroform