Pathological excretion patterns of urinary proteins in renal cell cancer patients exposed to trichloroethylene

Abstract

A study was carried out to investigate urinary protein excretion patterns by means of SDS-polyacrylamide-gel-electrophoresis (SDS-PAGE) in renal cell cancer patients who had previously been exposed to high levels of trichloroethylene. Thirty-eight out of 41 (93%) renal cell cancer patients investigated had former extensive trichloroethylene exposure, but only 23 out of 50 (46%) renal cell cancer patients without a history of occupational exposure to trichloroethylene revealed urinary protein patterns indicative of toxic effects on the tubular system. One hundred controls without histories of overt renal disease and not occupationally exposed to trichloroethylene were examined in the same way; only 11 (11%) of them displayed protein excretion patterns indicative of damage to the renal tubule. These results are supported by alpha 1-microglobulin excretion data. The following conclusions are drawn: (1) Substantially more cases of tubular damage are found amongst renal cell carcinoma patients having been exposed to substantial levels of trichloroethylene over many years as compared with renal cell carcinoma patients not exposed to trichloroethylene. (2) The results support the view that chronic tubular damage is a precondition for the nephrocarcinogenic effect of trichloroethylene. (3) The findings indicate that urine protein patterns, on the basis of the SDS-PAGE methodology, represent a 'biological effect parameter' for the medical surveillance of persons occupationally exposed to trichloroethylene.

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).…”

“…By this way, urine samples of at least 5 ml were obtained from 99 of the 134 cases (74%), and 299 of the 401 controls (75%) reported by Bru¨ning et al (2003). a 1 -Microglobulin determination As it was the intention of the present study to investigate the applicability of urinary a 1 -microglobulin as a parameter for the routine surveillance of exposed workers, it was considered appropriate for the standard nephelometric method (Boehringer), as in the preceding studies by Bru¨ning et al (1999aBru¨ning et al ( , 1999b, to be used. The detection limit of this routine method was 5 mg/l.…”

“…However, there was compelling evidence that the full development of a malignant tumour requires continued promotional stimuli, by repetitive episodes of high peak exposures to trichloroethylene over a prolonged period of time, leading to nephrotoxicity. The latter process is visualised by the excretion of tubular marker proteins in the urine of exposed persons (Bru¨ning et al 1999a(Bru¨ning et al , 1999b.…”

“…-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.…”