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White suckers (Catostomus commersoni) are one of two species of bottom-feeding fish in which various liver neoplasms are more prevalent in urban/industrial sites in western Lake Ontario than in less polluted sites in the Great Lakes. Previous studies indicate that white suckers excrete metabolites of various polycyclic aromatic hydrocarbons (PAHs) in bile, and that glutathione transferase (GST)-mediated conjugation is a major detoxification pathway for the PAH benzo[alpha]pyrene. To determine whether hepatocarcinogenesis in these wild fish is associated with induced GST-dependent resistance to carcinogens, we examined the expression of immunoreactive GSTs in liver neoplasms and putatively preneoplastic altered hepatocellular foci from white suckers collected from several polluted sites in western Lake Ontario. Histological sections of liver with altered hepatocellular foci, hepatocellular adenomas, hepatocellular carcinomas, bile duct adenomas and bile duct carcinomas were examined for GST immunoreactivity by the peroxidase-antiperoxidase (PAP) technique with polyclonal antiserum specific for all major GST isoenzyme subunits found in normal liver of white suckers. All bile duct adenomas, bile duct carcinomas and hepatocellular carcinomas were markedly or completely deficient in immunoreactive GST in comparison with surrounding normal hepatocytes. The majority of the hepatocellular adenomas were also deficient. Most altered hepatocellular foci had normal GST staining, but several GST-deficient altered hepatocellular foci were observed. However, none of the preneoplastic or advanced liver neoplasms expressed induced GST, suggesting that carcinogenesis is not associated with selection for GST-dependent resistance. Loss of hepatocellular GSTs may be incidental to neoplastic progression in these fish, or might be important in increasing susceptibility of some preneoplastic populations of hepatocytes to further DNA damage by environmental or endogenous chemicals that are normally detoxified by GSTs.

The expression of immunoreactive glutathione S-transferase (GST) was examined in hepatic neoplasms induced in rainbow trout by aflatoxin B1 (AFB) or 1,2-dimethylbenzanthracene (DMBA). Tumors were induced in adult trout by continuous dietary exposure to 8 p.p.b. AFB1 for 12 months or embryo bath exposure to DMBA (5 p.p.m. for 24 h, 3 times with 12 h intervals between exposures). Polyclonal antiserum specific for the two major trout hepatic GST subunits in trout liver was produced by immunizing rabbits with affinity-purified trout GST. Hepatocellular, cholangiolar and mixed neoplasms as well as foci of hepatocellular alteration were examined for GST immunoreactivity by the PAP technique. The majority of lesions were GST-deficient (AFB treated, 67%; DMBA treated, 54%), whereas GST expression was induced in 21% (AFB treated) and 31% (DMBA treated) of altered hepatic foci. The GST-induced foci were consistently small (AFB treated, 0.07 +/- 0.05 mm2; DMBA treated, 0.02 +/- 0.01 mm2) and none had progressed beyond the altered focus stage. The majority of larger advanced lesions (adenomas and carcinomas) were GST deficient (AFB treated, 2.33 +/- 0.35 mm2; DMBA treated, 2.95 +/- 0.59 mm2). These studies demonstrate that induced GST expression occurs in some small populations of hepatocytes, but not in larger advanced stages of malignant progression of aflatoxin- or PAH-induced hepatic neoplasms in rainbow trout.

Abstract. Male and female Wistar rats 2 to 15 months of age were inoculated intranasally with sialodacryoadenitis (SDA) virus and killed at 8 to 2 1 days post-inoculation (PI). Submandibular glands were evaluated by light and electron microscopy, and levels of salivary gland epidermal growth factor (EGF) were quantitated by cytochemistry and competitive radioreceptor assay. Apical granules in the epithelial cells of the granular convoluted tubules (GCT) were selectively depleted during the acute and convalescent stages of the disease. In addition, levels of immunoreactive EGF were reduced in affected submandibular glands, especially at 8 to 14 days PI with SDA virus, but some evidence of EGF depletion was seen at up to 3 weeks PI. A corresponding transient depletion of EGF receptor reactive salivary EGF was seen between 1 and 3 weeks after experimental SDA infection. These studies suggest that a clinical (or subclinical) infection with SDA virus could have significant effects on experimental studies on EGF-dependent functions, including reproductive physiology and carcinogenesis.In 1962, Cohen isolated a protein from mouse submandibular salivary glands which, when injected into newborn mice and rats, accelerated incisor eruption and eyelid ~p e n i n g .~ Referred to as epidermal growth factor (EGF), this protein is secreted primarily by the granular convoluted tubule (GCT) cells of the submandibular glands of mice and r a t~.~J~J~ EGF has also been demonstrated in minute quantities in various epithelial cells including renal tubules, Brunner's glands, and serous glands of the nasal cavity.6,20 EGF receptors have also been identified in a variety of tissues.6 EGF isolated from the mouse salivary glands is a polypeptide chain that chemically is closely related to EGF in rats and humans.2x22 This substance may be secreted directly by GCT cells into the circulation, but there is evidence that it is secreted into salivary gland collecting ducts, then reabsorbed in the gastrointestinal tract by receptor-mediated endocytosis. l 7 While it is secreted in an exocrine fashion,20 it has pleotrophic effects on many cell types much like endocrine polypeptide hormones. In mice, levels of salivary EGF are greater in males than in females,2 but in the rat, the amounts of EGF as determined by radioimmunoassay appear to be similar in the submandibular glands of both sexes.I0 Treatment with testosterone increased levels of EGF in submandibular salivary glands in both male and female rats.I0The physiological role of salivary EGF in rodents is not fully understood but it clearly influences carcinogenesis and reproductive function in mice. The incidences of spontaneous mammary tumors in intact and sialoadenectomized virgin mice at 1 year were approximately 62% and 13%, respectively. l 5 In addition, sialoadenectomy in mammary tumor-bearing mice caused a rapid and sustained cessation of tumor growth, but subsequent treatment with EGF restored the previous rate of groWth.I5 Similarly, removal of the submandibular salivary glands in fe...

To further characterize the putative role of constitutive and inducible plasma proteins in innate resistance to furunculosis, the present authors compared the alterations in profiles of plasma proteins in resistant and susceptible salmonids, i.e. rainbow trout, Oncorhynchus mykiss (Walbaum), and brook trout, Salvelinus fontinalis (Mitchill), respectively. Rainbow trout were injected with prednisolone acetate and exposed to higher water temperature (18 °C versus 10 °C), or injected with purified lipopolysaccharide (LPS) from a virulent strain of Aeromonas salmonicida, and plasma components were examined by two‐dimensional polyacrylamide electrophoresis. Two days after A. salmonicida LPS exposure, rainbow trout had a four‐ to five‐fold increase in concentrations of plasma proteins composed of p48, p19 and p16 subunits, and a significant decrease in a 100‐kDa protein group. Consistent elevation or depletion of proteins corresponding to previously reported rainbow trout A. salmonicida LPS‐binding pentraxins and lectins in plasma were not observed. Brook trout exposed to A. salmonicida LPS did not have any consistent plasma protein changes. There were no significant alterations in major plasma proteins following temperature shock and prednisolone acetate administration in rainbow trout plasma. These studies demonstrate that rainbow trout with LPS‐induced sterile inflammation have few alterations in major plasma proteins or LPS‐binding proteins, and do not exhibit the spectrum of acute phase changes induced by inflammation in mammals.