Acetaldehyde adducts in blood and bone marrow of patients with ethanol-induced erythrocyte abnormalities

Background: Although alcohol abuse is known to cause a wide array of advers e effects on blood cell formation, the molecular mechanisms by which alcoho l exerts its toxic actions remain poorly defined. We examine here the forma tion of acetaldehyde-derived protein modifications in erythrocytes and in t heir bone marrow precursors using antibodies specifically recognizing aceta ldehyde-modified epitopes in proteins independently of the nature of the ca rrier protein. Materials and Methods: We studied 138 consecutive adult patients undergoing bone marrow aspiration due to macrocytosis (MCV values above 99 fL). Asses sment included complete blood counts, morphologic review, assessment of alc ohol consumption, and biochemical and immunocytochemical assays for acetald ehyde adducts. Results: There were 68 patients (49%) with a history of excessive alcohol c onsumption, 28 (20%) of whom were patients with severe dependence. The bloo d smears prepared from the alcoholic patients with macrocytosis also contai ned stomatocytes and knizocytes. Bone marrow aspirates from 12 alcoholic pa tients showed vacuolization of pronormoblasts and the presence of ring side roblasts was noted in 8 cases. In immunocytochemical analyses of the periph eral blood erythrocytes, acetaldehyde-derived epitopes were found to occur both on the cell membrane and inside the erythrocytes. Bone marrow aspirate s also showed positive staining for acetaldehyde adducts in the erythropoie tic cells in 8 of 11 (73%) consecutive alcoholic patients. Separation of th e erythrocyte proteins from the samples of alcoholics on HPLC-chromatograph revealed the formation of fast-eluting hemoglobin fractions, which also re acted with antibodies against acetaldehyde adducts. Conclusions: Current data suggest that acetaldehyde-erythrocyte adducts are formed in vivo in blood and bone marrow of patients with excessive alcohol consumption. This may contribute to the generation of the erythrocyte abno rmalities, which are frequently observed in alcoholic patients.