Concentration-dilution of spot urine samples is a shortcoming of the biological monitoring of industrial xenobiotics. To ascertain whether the adjustment of urinary cadmium measured in spot samples is appropriate, urine samples were taken three times, once a week for 3 successive weeks, from 25 welders employed in the manufacture of jewelry (total 75 samples). Cadmium, creatinine, specific gravity, total urinary solutes, urinary volume and urinary flow rate were measured in 12-h collections and in spot samples taken immediately afterwards. Creatinine and total urinary solutes showed high inverse correlation with urinary flow rate (r = -0.858 and r = -0.768 respectively). Urinary cadmium displayed a similar trend but the correlation was not significant (r = -0.145). Creatinine adjustment of urinary cadmium values in spot samples increased the correlation with the same index in timed samples adjusted for urinary volume (r = -0.808) or urinary flow rate (r = 0.821) compared with non-adjustment (r = 0.732 and r = 0.738, respectively). Creatinine adjustment of spot sample values is also suitable for a wide range of urinary concentrations; discarding excessively diluted or concentrated urines, correlation of urine samples improved for non-adjusted or specific gravity-adjusted values, whereas no changes were observed for creatinine-adjusted values.

The contribution of testosterone to the nephrotoxic effects of 1,2-dichloropropane (DCP) was assessed by a series of castration and sex hormone replacement experiments on Wistar rats. The nephrotoxic action of DCP was evaluated by measuring the accumulation of organic anion and release of aspartate aminotransferase into the incubation medium using a renal cortical slice model. Our data show that sex, castration, and testosterone pretreatment are factors that influence the effect of DCP on renal cortical slices of rats Males appear to be more sensitive to nephrotoxic effects of DCP than females, male castration prevents the nephrotoxic effects of DCP, and pretreatment of females and castrated males with testosterone increases the susceptibility to DCP. In this study an attempt was made to evaluate the role of sex differences in the expression of enzymes participating in Phase I and Phase II detoxication reactions in order to explain the differences in sensitivity of the two genders to the nephrotoxic action of DCP. Our results implicate gender-specific expression of cytochrome P-450 in the kidneys as a predominant factor that determines the different susceptibilities of male and female rats to the nephrotoxic effect of DCP. We propose that the oxidation of DCP by CYP IIE1 is the first saturable and limiting step in the metabolic activation of DCP to nephrotoxic metabolites. It appears that, despite the fact that the nephrotoxic effect of DCP is determined mainly by its cysteine-conjugated metabolites, gluthathione (GSH) content and glutathione S-transferase (GST) activity in kidney are not directly related to increased androgen-related susceptibility to DCP.(ABSTRACT TRUNCATED AT 250 WORDS)

Sex- and age-related nephrotoxicity due to 1,2-dichloropropane was studied in vitro by means of renal cortical slices obtained from Wistar rats. Reduced glutathione content, organic anion accumulation (p-aminohippurate), and release of malondialdehyde (to measure the extent of lipid peroxidation), aspartate aminotransferase, gamma-glutamyltransferase and lactate dehydrogenase into the incubation medium were determined. Sex differences in naive rats parameters were slight, but male were more susceptible to toxic effects of 1,2-dichloropropane than female rats; glutathione depletion, lipid peroxidation, and loss of organic anion accumulation were higher in male than in female slices. During senescence, naive male rats showed a progressive decrease of glutathione content (statistically significant from 7-9 months of age), increase of spontaneous lipid peroxidation from the same age, and increase of signs of cytotoxicity (release of aspartate aminotransferase and lactate dehydrogenase into the incubation medium) from 3-4 months of age. A loss of organic anion accumulation started from 7-9 months of age. Slices from rats of 3-4 months old showed the apparently highest susceptibility to 1,2-dichloropropane but depletion of glutathione content and loss of organic anion accumulation were at the same level in the oldest rats. The age decrease of control values caused the differences in the percentage ratio and then, apparently, a lower DCP effect. On the contrary, the increase of aspartate aminotransferase released in the incubation medium by DCP-treated slices corresponded to the age-related increase in cytotoxicity.

The possibili that urinary glutamine transaminase K activity might be a marker of a proximal tubule segment-specific response to mercuric chloride was investigated in male rats after a single i.p. injection in time-course and dose-response experiments. Urinary total proteins and angiotensin converting enzyme activity were determined simultaneously. Urinary indices showed an early increase (within 5 h of treatment) of total proteins and angiotensin converting enzyme, whereas glubmine transaminase K increased 10 h after treatment. The peak of all these indices was observed 24 h after mercuric chloride injection. The lowest dose that induced a significant increase in proteins and enzymes was 0.25 mg kg(-1); in addition, a dose-response effect was observed. Glutamine transaminase K appeared to be an early and sensitive index of response of mercuric chloride effects, similar to total proteins and angiotensin converting enzyme. It is suggested that this enzyme is mainly localized in the 'pars recta' of the proximal tubule. Therefore glutamine transaminase K might be a segment-specific marker for the detection of damage localized in this portion of the proximal tubule.

Release of some cytosolic (aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase) and brush border (y-glutamyltransferase and alkaline phosphatase) enzymes from renal cortical slices was studied in vitro. Renal cortical slices were prepared freehand from 3-month-old male and female Wistar rats of different hormonal status. Some male and female rats were castrated at 1 month of age and a portion of castrated males and of naive males and females were S.C. treated with testosterone (10 mg kg-' body wt.) on alternate days for 3 weeks. Females had higher alanine aminotransferase (77.5 f 2.8 nmol 100 mg-' tissue), lactate dehydrogenase (5.01 2 0.24 Fmol) and alkaline phosphatase (1.63 f 0.15 mol) activities than male rats (20.4 f 0.9, 3.99 f 0.19 and 0.91 f 0.02, respectively). On the contrary, aspartate aminotransferase and y-glutamyltransferase were similar. Among cytosolic enzymes, alanine aminotransferase and lactate dehydrogenase appeared to be sexual hormone-dependent enzymes: castration significantly increased enzyme activities in males (49.6 f 1.1 for the former; 5.30 rf: 0.15 for the latter) and caused significant decreases in females (alanine aminotransferase only 47.1 f lS), whereas testosterone pretreatment decreased activities in cortical slices from female (48.1 * 3.6 and 3.81 f 0.07, respectively) and castrated male (27.4 rf: 1.8 and 4.05 rf: 0.15, respectively). Moreover, exogenous testosterone increased aspartate aminotransferase in males (1.05 f 0.01 pmol) and castration increased it in both sexes. The activity of brush border enzymes was increased by testosterone pretreatment and decreased by castration (mainly alkaline phosphatase).