Distribution of polychlorinated biphenyls and chlorinated pesticide residues in trout in the Sierra Nevada.

Organochlorine compounds are known to be atmospherically transported to long distances from their original sources. To understand the influence of California's Sierra Nevada range on the air transport and subsequent distribution pattern of some of these residues within the range, we have chosen salmonid fish as an indicator species. Fish were collected from 10 locations throughout the northern and central Sierra Nevada and polychlorinated biphenyl (PCB), toxaphene, chlordane, and DDT [1,1,1-trichloro, 2,2'-bis (p-chlorophenyl) ethane] residues in muscle tissue were analyzed. Rainbow trout (Oncorhynchus mykiss) were found in all sampling locations, and therefore analyses mainly focused on this species. When similar-sized rainbow trout samples from several similar oligotrophic, high-altitude lakes and streams were compared, it became apparent that altitude is one of the factors affecting the residual levels of PCB (r(2) = 0.882), but not for total DDT, toxaphene, or chlordane in trout. Analysis of correlations among these four organochlorine compound residue groups indicated that there are modest correlations in patterns of distribution between chlordane vs. toxaphene (r(2) = 0.345), and chlordane vs. total DDT (r(2) = 0.239), but toxaphene residues are not correlated with PCB or total DDT. In view of significant correlation to the altitude it is concluded that PCB residue in rainbow trout is a good monitoring tool for studying the effect of high-altitude mountain ranges on the long-range transport and distribution of those persistent pollutants.

Correlation between the high expression of C/EBPbeta protein in F442A cells and their relative resistance to antiadipogenic action of TCDD in comparison to 3T3-L1 cells.

We compared the ability of two clonally derived murine preadipocyte cell lines, 3T3-L1(L1) and 3T3-F442A (F442A), to differentiate after treatment by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and found that the former cell line was clearly suppressed by TCDD but the latter was not. It was initially postulated that the easiest way to explain the lack of response to TCDD in F442A cells could be an alteration in aryl hydrocarbon receptor (AhR) functionality. This hypothesis was tested first, but no differences were found in the levels or functions of AhR. To find an alternate explanation for such a differential effect of TCDD, we tested the action of several diagnostic agents on the process of adipocyte differentiation of these two cells. No differences were found between these two lines of cells in the susceptibility to the antiadipogenic action of 12-0-tetradecanoylphorbol-13-acetate (TPA), or to TNFalpha, indicating that the basic biochemical components engaged in the antiadipogenic actions of these agents in these two cell lines are similar. In contrast, F442A cells were found to be more resistant to the antiadipogenic action of EGF or TGFbeta than L1 cells which were tested side by side. Based on the knowledge that TNFalpha preferentially affects C/EBPalpha and that TGFbeta specifically controls C/EBPbeta and delta in their antiadipogenic action, we hypothesized that the major cause for the differential response of these two similar cell lines could be the insensitivity of C/EBPbeta and/or delta of F442A cells to the action of TCDD. We could obtain supporting data for this hypothesis, showing that in F442A cells, the level of C/EBPbeta is already high even before the addition of adipocyte differentiation factors and that TCDD did not cause any significant changes in the titer of C/EBPbeta.

Effects of src-deficiency on the expression of in vivo toxicity of TCDD in a strain of c-src knockout mice procured through six generations of backcrossings to C57BL/6 mice.

The effect of TCDD was studied in c-src-deficient C57BL6-src(tm1sor) (N6 src -/- and -/+) mice, and their wild-type littermate mice (N6 src +/+). The former was created from the original strain of B6, 129-src(tm1sor) mice through six generations of backcrossings with C57BL6 mice. The results of a high dose TCDD toxicity tests in male mice indicated that N6 src-/+ mice were significantly less responsive to the toxic action of TCDD (115 microg/kg single i.p. injection) than N6 src+/+ mice in terms of reduced % body weight gain, the increase in the liver to body weight ratio, and the decrease in the adipose tissue to liver weight ratio and in the weight of pancreas. To understand the cause for these differential effects of TCDD we studied TCDD-induced changes in several biochemical parameters at day 10 and found that most drastically affected ones were glycogen depletion and phosphoenolpyruvate carboxykinase (PEPCK) downregulation. In addition, the degree of triglyceride accumulation in liver was less pronounced in N6-/+ than in N6+/+ mice. These findings suggest that the absence of c-src expression indeed affects the development of selected, TCDD-induced toxic endpoints that are related to wasting syndrome.

Estrogenic action of ß-HCH through activation of c-Neu in MCF-7 breast carcinoma cells.

ß-HCH is known to be a poor agonist for the estrogen receptor (ER), and yet it has been shown to act like an estrogen in stimulating foci formation in MCF-7 cells. We investigated the reason for such an action of ß-HCH, using a rat prolactin-luciferase reporter system transfected to MCF-7 cells. We found that the presence of c-Neu (erbB2), ER and ERE is needed for ß-HCH to act estrogenic at the transcription activation level in this cell line. We compared the action of ß-HCH to that of EGF which is known to act estrogenic without being an agonist for ER in this cell and found that their action patterns are quite similar, the only difference being that the former action is blocked by an antibody against c-Neu and the latter by both c-Neu and EGF receptor antibody. We concluded that ß-HCH's estrogenic action in this cell model is mediated through "ligand-independent activation of ER pathway".