Benzyl alcohol alters the hemoglobin phenotype of mouse erythroleukemia cells

The hemoglobin minor/hemoglobin major ratio expressed in mouse erythroleukemia (MEL) cells grown in vitro varies according to the differentiation inducer utilized. For example, butyrate and hemin induce higher hemoglobin minor/hemoglobin major ratios than do dimethyl sulfoxide (DMSO) or hexamethylene bisacetamide (HMBA). Benzyl alcohol in non-toxic concentrations was found to markedly reduce the hemoglobin minor/hemoglobin major ration and to moderately reduce the total hemoglobin induced by DMSO or HMBA in MEL cells, while only slightly decreasing the ratio induced by hemin or butyrate. The addition of dexamethasone (another and more potent inhibitor of the induction of hemoglobin synthesis than benzyl alcohol) to the media during HMBA induction of differentiation increased the hemoglobin minor/hemoglobin major ratio. This is similar to other 'inhibitory' treatments (i.e., treatments that result in sub-optimal hemoglobin production) that have been previously reported. Therefore, although benzyl alcohol and dexamethasone both partly inhibit the induction of total hemoglobin production, they have opposite effects on the induced hemoglobin phenotype: benzyl alcohol decreases the hemoglobin minor/hemoglobin major ratio while dexamethasone increases it. The mechanism(s) of the alteration in the hemoglobin phenotype is unknown as is the mechanism of induction by any of the various inducing agents or of the inhibition of induction by any treatment. However, it appears that if the signal for the induction of hemoglobin minor is sufficiently potent (as it is during butyrate or hemin induction), it cannot be overcome by benzyl alcohol at a 'non-toxic' concentration.