title: Cutaneous xenobiotic metabolism: glycine conjugation in human and rat keratinocytes.
abstract: Glycine conjugation is an important route of metabolism and detoxication of carboxylic acids in the liver. In this paper the in vitro cutaneous metabolism of [carboxyl-14C]benzoic acid to its glycine conjugate hippuric acid in rat and human skin is reported. Cutaneous glycine conjugation was studied in F344 rat and human epidermal keratinocytes using two systems: (1) freshly isolated keratinocytes in suspension and (2) primary keratinocyte cultures. For comparative purposes, studies were also carried out in freshly isolated and cultured F344 rat hepatocytes. After incubation of 5 x 10(6) cells with 1 microM benzoic acid at 37 degrees C for 8 hr, no glycine conjugation was observed in rat and human keratinocyte suspensions, with greater than 98% of the radioactivity recovered as the parent compound. In contrast, cultured keratinocytes exhibited glycine conjugation, with 10.9 +/- 1.0% (mean SEM, n = 3) and 2.1 +/- 0.6% (mean SEM, n = 3) conversion to hippuric acid at 8 hr in rat and human cells, respectively. Tissue-specific differences in metabolism were observed, with conjugation in hepatocytes significantly greater (P < 0.05) than in keratinocytes at all times up to 8 hr. After incubation of benzoic acid with cultured hepatocytes for 8 hr, more than 98% of the of the radioactivity was recovered as the glycine conjugate. These studies indicate that rat and human skin possesses low, but demonstrable, glycine-conjugating activity, and that keratinocytes in primary culture may provide a better system than freshly isolated cell suspensions for studying such activity.
authors.affiliation: Imperial College School of Medicine, St Mary's, London, UK.
authors.forename: P
authors.initials: P
authors.lastname: Nasseri-Sina
authors.forename: S A
authors.initials: SA
authors.lastname: Hotchkiss
authors.forename: J
authors.initials: J
authors.lastname: Caldwell
mesh_terms: D000328:Adult; D000818:Animals; D001565:Benzoates / Q000378:metabolism; D019817:Benzoic Acid; D002478:Cells, Cultured; D005260:Female; D005998:Glycine / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011247:Pregnancy; D051381:Rats; D011916:Rats, Inbred F344; D012867:Skin / Q000166:cytology / Q000378:metabolism*; D013045:Species Specificity
chemical_list: D001565:Benzoates; D019817:Benzoic Acid; D005998:Glycine