Preexistence of chronic tubular damage in cases of renal cell cancer after long and high exposure to trichloroethylene

Abstract

Substantially more cases of tubular damage were found among renal cell carcinoma patients who had been exposed to high levels of trichloroethylene over many years than among renal cell carcinoma patients who had not been exposed to trichloroethylene. This supports the hypothesis (Goeptar et al. 1995) that chronic tubular damage may be regarded as a necessary precondition for trichloroethylene to exert a nephrocarcinogenic effect. The findings also indicate that the urine protein patterns identified with SDS-PAGE may represent a valuable parameter for effect biomonitoring of persons exposed to high levels of trichloroethylene over many years.

Urinary a 1 -microglobulin excretion as biomarker of renal toxicity in trichloroethylene-exposed persons

“…This difference in exposure histories very well explains the apparent divergence between the results of Green et al (2004) and those of the present study. On the other hand, the present data are entirely consistent with our previous reports concerning nephrotoxicity in persons highly exposed to trichloroethylene (Bru¨ning et al 1996(Bru¨ning et al , 1999a(Bru¨ning et al , 1999b. Only 52% of renal cancer cases not reporting exposures to trichloroethylene showed normal excretions of a 1 -microglobulin.…”

“…This concern was primarily based on findings of increased incidences of renal cell cancers (Vamvakas et al 1998), accompanied by specific somatic mutations in the VHL tumour suppressor gene (Brauch et al 1999), in persons with long-lasting and high occupational exposures to trichloroethylene. Consistent with both human (Bru¨ning et al 1996(Bru¨ning et al , 1999a(Bru¨ning et al , 1999b and experimental animal data (Mensing et al 2002;McGoldrick et al 2003), it was postulated that the nephrocarcinogenicity of trichloroethylene is a highdose phenomenon. A theoretical concept was developed that was based on a synopsis of all experimental, clinical and epidemiological data (Bru¨ning and Bolt 2000).…”

“…-Urinary protein profiling using SDS-PAGE (for screening; Bru¨ning et al 1996) -a 1 -Microglobulin excretion (Bru¨ning et al 1999a) -Glutathione S-transferase excretion (Bru¨ning et al 1999b) On the basis of stability of parameter and general availability of a simple analytical method, it has been recommended that a 1 -microglobulin excretion, as a routine parameter in the occupational practice (DFG 2003), be primarily used.…”

Biological monitoring of kidney function among workers occupationally exposed to trichloroethylene

“…GST-a (mg/g) 6 exposure, these two individuals being exposed to 113 and 153 ppm respectively. The combined concentrations of the oxidative metabolites of trichloroethylene, trichloroethanol, and trichloroacetic acid, in the same individuals were 400 and 1333 mg/ml respectively.…”

“…5 In support of the belief that exposures were extremely high in the German studies, a number of reports identifying kidney damage within the exposed populations have been published. [5][6][7][8][9][10] As with the cancer studies direct evidence of exposure is lacking. Furthermore, these studies measured a number of sensitive urinary markers of kidney dysfunction, including several microglobulins, retinol binding protein, and glutathione Stransferase a, which vary widely within the normal human population and are affected by age and sex, by a wide range of lifestyle factors including smoking and exercise, and by a wide variety of disease states and drug therapies.…”