Histologic localization of serum constituents, Ca-45(2+), Cl-36(-), [C-14]urea, and [S-35]cysteine in forming hair after systemic administration

Abstract

To further investigate the chemical mechanisms involved in the accumulation of drugs or other compounds in hair, we characterized histologically the deposition of radiolabeled serum constituents in the hair of BALB/c (albino) and C57 (pigmented) mice. The extent and location of the incorporation of a normal serum cation (Ca-45(2+)), a serum anion (Cl-36(-)), a neutral constituent ([C-14]urea), and a structural component of hair ([S-35]cysteine) were studied to provide a comparative framework for the examination of drugs deposited in hair from serum. Two mouse strains were used to evaluate the effect of hair pigmentation on deposition. Localization of deposition was observed using microautoradiography of skin sections from animals given a systemic dose of each tracer. The cation, Ca-45(2+), associated with melanocytes and melanosomes of forming C57 hair within 5 min of dosing, but did not associate with the cells of forming BALB/c hair. This was consistent with previous results that indicated greater concentrations of Ca2+ in mature C57 mouse hair when compared with mature BALB/c hair. Both [C-14]urea and [S-35]cysteine associated with all cells in the papilla of the forming hair of both C57 and BALB/c mice. This again was consistent with previous results that indicated that similar concentrations of cysteine and urea were incorporated into mature C57 and BALB/c hair. The anion, Cl-36(-), did not associate with either C57 or BALB/c hair. The lack of deposition of Cl-36(-) may be due to the loss of the tracer during sample processing and suggests that Cl- could be removed from mature hair. These data confirm previous results that suggested that the melanin component of hair was capable of ionic interactions and that the protein component was capable of neutral, lipophilic interactions. Our findings suggest a multicompartmental model of drug deposition in hair