Cullen M R, Solomon L R, Pace P E, Buckley P, Duffy T P, McPhedran P, Kelsey K T, Redlich C A
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
Environ Res. 1992 Oct;59(1):250-64. doi: 10.1016/s0013-9351(05)80244-0.
In a previous cross-sectional survey, up to 15% of shipyard painters were found to have mild anemia or granulocytopenia, mostly acquired since employment. Environmental studies had suggested a possible etiologic role for ethylene glycol ethers, solvents to which the men were heavily exposed and which have established myelotoxic potential. To exclude alternative hypotheses, examine possible common patterns of injury, and identify potential risk factors and markers for such an effect, the affected painters were further studied. The painters were matched with two groups of controls: exposed painters without evidence of hematologic abnormality on the previous survey and unexposed controls. Altogether 25 subjects were studied by histopathologic examination of bone marrow, cytogenetic studies of marrow cells, and peripheral lymphocytes and peripheral red cell studies of membrane and metabolic function. Except for an unexpected finding of a race-associated effect on marrow histology, insignificant differences were seen among the groups in terms of marrow morphology and cellularity, stem cell growth kinetics, and marrow or peripheral cytogenetics. Two metabolic abnormalities of peripheral red cells related to exposure or clinical status of the subjects were found. Pyruvate kinase, an established marker of acquired myelodysplasia, was significantly depressed in the subjects with previously abnormal counts. Although reduced glutathione levels and holoenzyme activities of glutathione reductase (GSHR) did not differ among groups, exposed subjects had decreased saturation of GSHR with flavin adenine dinucleotide which could be restored in vitro, suggesting riboflavin deficiency or impaired riboflavin metabolism. Thus, although a unique pattern of bone marrow injury by histologic or genetic assay attributable to ethylene glycol ethers was not defined, biochemical effects of possible mechanistic importance were identified. The relevance of these findings as subclinical disease markers remains to be established.
