Influence of metabolic genotype GSTM1 on levels of urinary mutagens in patients treated topically with coal tar

Fifteen hospitalized, non-smoking, dermatological patients were treated wit h ointment containing 2% coal tar (CT) in order to assess the influence of metabolic genotype GSTM1 on urinary mutagen levels. Urinary 1-pyrenol, the main metabolite of pyrene, was used to check the high exposure to PAH of th is population. The mean levels of urinary 1-pyrenol found in the 24-h urine of our patients were 467.8 +/- 211.0 nmoles-24 h (range 94.6-890.1 nmoles- 24 h). Mutagenicity was assessed on urine samples collected over a period o f 24 h, after three consecutive days of topical application, using the bact erial mutagenesis test on Salmonella typhimurium strains TA98 and YG1024 in the presence of microsomal enzymes. The latter strain turned out to be mor e sensitive than the former in revealing urinary mutagens in these patients (42 693 +/- 30 867 vs. 6877 +/- 6040 net revertants-24 h). The mutagenicit y on YG1024 strain and 1-pyrenol levels of urine samples were correlated (S pearman's rank correlation coefficient = 0.6678, P < 0.01, z = 2.795). The influence of genotype GSTM1 on urinary mutagen levels was assessed on strai n YG1024. The values of urinary mutagenicity of subjects with genotype GSTM 1-null (n = 6) were on average higher than those of GSTM1-positive subjects (n = 9) (55 498 +/- 45 957 vs. 34 156 +/- 11 933 net rev.-24 h), a non-sig nificant statistical difference. The mean total excretion of mutagens corre cted for PAH exposure (net rev./nmoles of urinary 1-pyrenol) in GSTM1-null patients was double that of GSTM1-positive ones (136.8 +/- 34.7 vs. 70.8 +/ - 23.3 net rev./nmoles of urinary 1-pyrenol; one-tailed Mann-Whitney U-test , U = 11.5, P < 0.05). These results indicate a greater body burden of prom utagens, resulting from skin application of CT, in GSTM1-null subjects. (C) 1999 Elsevier Science B.V. All rights reserved.