Reaction of 14C-acetaldehyde with whole blood in vitro: further evidence for the formation of unstable complexes with plasma proteins and red cells.
When heparinised whole blood was incubated with 5, 10, 45 or 180 microM 14C-acetaldehyde for 1 hr, an average of 33%, 34%, 33% and 41%, respectively, of the radioactivity was associated with red cells and the remainder with plasma. Although 71-80% of the radioactivity in the plasma was TCA-precipitable, only 0.9-3.1% was non-dialysable after 48 hr of dialysis, indicating that much of the acetaldehyde was reversibly bound to protein. When blood was incubated with 10-180 microM 14C-acetaldehyde for 1 hr and the plasma subjected to Sephacryl S300 gel filtration, 0.3-1.9% of the added radioactivity was found in the albumin and IgG fractions; this radioactivity is presumed to reside in both unstable and stable acetaldehyde-protein adducts. Plasma derived from whole blood which was incubated with 5-180 microM acetaldehyde and dialysed for 24 hr displayed cytotoxic activity against A9 cells. These data indicate that when 14C-acetaldehyde is incubated with whole blood, even at concentrations as low as 5-10 microM, a substantial proportion of the radioactive molecules form unstable cytotoxic adducts with plasma proteins and a much smaller proportion form stable adducts. Blood cells (mainly red cells) that were incubated with 14C-acetaldehyde were able to transfer radioactivity to cocultured K562 cells, supporting the possibility that not only acetaldehyde-modified plasma proteins but also acetaldehyde-modified blood cells may transport acetaldehyde and be cytotoxic in vivo.
Wickramasinghe
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Department of Haematology, St Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London, U.K.
Thomas
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Hasan
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D000079:Acetaldehyde / Q000493:pharmacokinetics* / Q000633:toxicity; D000818:Animals; D001798:Blood Proteins / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D011485:Protein Binding / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects
D001798:Blood Proteins; D000079:Acetaldehyde