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Toxicologic Pathology
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Journal Article

Lack of Effects of Viral Sialoadenitis and Depletion of Epidermal Growth Factor on Initiation of Hepatic Carcinogenesis in the Rat

Donald R. Kemp

Connaught Laboratories Ltd., Willowdale, Ontario, and

Dean H. Percy

Department of Pathology, Ontario Veterinary College, Guelph, Ontario

M. Anthony Hayes

Department of Pathology, Ontario Veterinary College, Guelph, Ontario

Sialodacryoadenitis (SDA) is a commonly-encountered coronaviral infection in laboratory rats that causes acute destruction of submandibular salivary glands. SDA results in depletion of salivary epidermal growth factor (EGF) and may thereby affect EGF-dependent cell growth processes. The purpose of this study was to determine the effects of SDA virus (SDAV) infection on the growth factor-dependent stages of experimental liver carcinogenesis. Rats were injected ip with the carcinogen diethylnitrosamine (DENA) at 1, 2, or 3 weeks following inoculation with SDAV. Uninfected control rats were treated only with DENA. The salivary glands of SDAV-inoculated and control rats were stained using the immunoperoxidase method for the detection of EGF. Residual submandibular salivary gland lesions and focal depletion of EGF were still evident in affected submandibular glands for up to 42 days after SDAV infection. Serum EGF concentrations measured at 9, 28, and 42 days following SDAV inoculation were reduced, but were not significantly different in comparison with non-inoculated, DENA-treated control rats. Initiated hepatocytes were detected 21 days after DENA treatment in formalin-fixed sections by an immunoperoxidase stain for the P isoenzyme of the enzyme glutathione S-transferase (GST-P). There was no significant difference in the number of foci of GST-P positive cells in a comparison of initiated cells in SDAV-inoculated and non-inoculated rats. Based on this model, concurrent infection with SDAV does not appear to have any significant effects on the initial stages of chemical hepatocarcinogenesis in the rat.

Key Words: Diethylnitrosamine • epidermal growth factor • glutathione S-transferase • immunoperoxidase • sialodacryoadenitis virus • submandibular salivary gland

Toxicologic Pathology, Vol. 19, No. 2, 156-163 (1991)
DOI: 10.1177/019262339101900210
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