SOFT/TIAFT 98 - Deposition and Retention of Radiolabeled Serum ....

SOFT - TIAFT 1998

Scientific Session 5

Thursday October 8, 1998

DEPOSITION AND RETENTION OF RADIOLABELED SERUM CONSTITUENTS IN HAIR FOLLOWING SYSTEMIC ADMINISTRATION
	Peter R. Stout, Donna Dehn* and James A. Ruth* University of Colorado Health Sciences Center, Department of Molecular Toxicology and Environmental Health Sciences, 4200 East Ninth Avenue, Box C238, Denver, CO, 80262, USA

To investigate the chemical mechanisms involved in the accumulation of drugs or other compounds into hair, we examined the deposition of radiolabeled serum constituents in the hair of Balb/C (albino) and C57 (pigmented) mice. The extent of in vivo incorporation of a normal serum cation ([⁴⁵Ca⁺⁺]), an anion ([³⁶Cl^-]), a neutral constituent ([¹⁴C]-urea) and a structural component of hair ([³⁵S]-cysteine) were studied to provide a reference framework for the examination of foreign substances deposited in hair from serum. The use of two mouse strains afforded an evaluation of the effect of hair pigmentation on levels of accumulation Additionally, the endogenous content of Mg⁺⁺, Na⁺and K⁺ (measured by ICP-AES) was determined, as was their susceptibility to removal. Hair concentration of isotopes were calculated from mean specific activities determined over the treatment period and corrected for quenching and decay.

[⁴⁵Ca⁺⁺] accumulation (500 ng/mg hair in C57 and 25 ng/mg hair in Balb/C) was unaffected by a 24 hr phosphate buffer extraction. Of the [¹⁴C]-urea accumulated (3,500 ng/mg in C57 and Balb/C), 50% was removed by 24 hour extraction in phosphate buffer. Of the accumulated [³⁶Cl^-] (65 ng/mg in C57; 30 ng/mg in Balb/C), half was removed by 24 hr extraction in phosphate buffer. The accumulated [³⁵S]-cys (210 ng/mg in C57; 110 ng/mg in Balb/C) could not be removed. Endogenous Mg⁺⁺ (350 ng/mg in C57; 75 ng/mg in Balb/C) was stable to 24 hr extraction in phosphate buffer. K⁺ (2,500ng/mg) and Na⁺ (400 ng/mg) concentrations were approximately equal in both strains and were largely extractable.

Based on the accumulation of a neutral serum constituent such as urea, the data suggest that factors other than ionic binding are important in deposition of circulating molecules into hair. The extent and reversibility of ionic binding is dependent upon the chemical nature of the substance. The presence of hair pigmentation greatly increased the accumulation of [⁴⁵Ca⁺⁺], [³⁶Cl^-] and [³⁵S]-cys. These data support a multicompartmental nature of drug storage in hair.

This work supported by NIH grant DA09545.

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