Pathological excretion patterns of urinary proteins in miners highly exposed to dinitrotoluene.
A cohort of 161 underground miners who had been highly exposed to dinitrotoluene (DNT) in the copper-mining industry of the former German Democratic Republic was reinvestigated for signs of subclinical renal damage. The study included a screening of urinary proteins excreted by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and quantitations of the specific urinary proteins alpha 1-microglobulin and glutathione-S-transferase alpha (GST alpha) as biomarkers for damage of the proximal tubule and glutathione-S-transferase pi (GST pi) for damage of the distal tubule. The exposures were categorized semiquantitatively (low, medium, high, and very high), according to the type and duration of professional contact with DNT. A straight dose-dependence of pathological protein excretion patterns with the semiquantitative ranking of DNT exposure was seen. Most of the previously reported cancer cases of the urinary tract, especially those in the higher exposed groups, were confined to pathological urinary protein excretion patterns. The damage from DNT was directed toward the tubular system. In many cases, the appearance of Tamm-Horsfall protein, a 105-kD protein marker, was noted. Data on the biomarkers alpha 1-microglobulin, GST alpha, and GST pi consistently demonstrated a dose-dependent increase in tubular damage, which confirmed the results of screening by SDS-PAGE and clearly indicated a nephrotoxic effect of DNT under the given conditions of exposure. Within the cluster of cancer patients observed among the DNT-exposed workers, only in exceptional cases were normal biomarker excretions found.
Brüning
T
T
Institut für Arbeitsphysiologie an der Universität Dortmund, Germany. bruening@bgfa.de
Thier
R
R
Mann
H
H
Melzer
H
H
Bröde
P
P
Dallner
G
G
Bolt
H M
HM
D015415:Biomarkers / Q000652:urine; D015331:Cohort Studies; D004136:Dinitrobenzenes / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004784:Environmental Monitoring; D062665:Epidemiological Monitoring; D005859:Germany, East / Q000453:epidemiology; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000652:urine; D006801:Humans; D007527:Isoenzymes / Q000652:urine; D007680:Kidney Neoplasms / Q000652:urine; D008562:Membrane Glycoproteins / Q000652:urine; D008906:Mining / Q000706:statistics & numerical data*; D016273:Occupational Exposure / Q000009:adverse effects* / Q000145:classification; D011507:Proteinuria / Q000139:chemically induced* / Q000145:classification / Q000453:epidemiology*; D012189:Retrospective Studies; D014360:Trypsin Inhibitor, Kunitz Soybean
D015415:Biomarkers; D004136:Dinitrobenzenes; D007527:Isoenzymes; D008562:Membrane Glycoproteins; C109148:SPINT2 protein, human; D014360:Trypsin Inhibitor, Kunitz Soybean; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C119995:glutathione S-transferase alpha