Effect of Thioacetamide on the Incorporation of [³H]-Thymidine into Dna of 13 Tissues and on the Mitotic Index of the Corneal Epithelium of Bd2F₁ in Male Mice while Taking into Consideration Circadian Variation

Abstract

An investigation was done to assess the effect of a single intraperitoneal (ip) injection of thioacetamide on the incorporation of [³H]TdR into DNA of 13 different tissues and on the mitotic index of the corneal epithelium of mice. Seven-week-old CD2F₁ mice, who had been standardized to 12 hours (hr) of light alternating with 12 hr of darkness, and fed ad libitum were used. The experimental design took into consideration the circadian variation that characterizes cell proliferation in all of the tissues studied. This was done by killing subgroups of seven animals every 6hr for 96 hr. Thirty minutes prior to killing all mice were injected ip with 25 μCi of [³H]-thymidine and its incorporation into DNA was determined. The tissues of all thioacetamide and saline treated mice showed marked circadian variation in DNA synthesis. Thioacetamide treatment brought about significant (P < 0.05) stimulation of DNA synthesis in the liver and kidney thus confirming, but extending an earlier finding. Moreover, the data showed for the first time that DNA synthesis in the bone marrow and spleen and colon were markedly statistically significantly stimulated at specific times after treatment. Synthesis of DNA in the thymus, lung, testes, tongue, esophagus, duodenum, rectum and the mitotic index in the corneal epithelium were not statistically significantly altered by thioacetamide treatment.

A preliminary study also was carried out to explore what effect multiple treatment with epidermal growth factor (EGF) had on DNA synthesis in thioacetamide treated mice. Mice were killed 36 hr after thioacetamide treatment, but were treated with EGF which began 15 hr after the thioacetamide was administered and this was repeated at 18, 21 and 24 hr (50 μg/mouse/treatment). Under the conditions of this study EGF significantly (P < 0.05) depressed DNA synthesis 76% in the liver, 64% in the thymus, 22% in the spleen, 30% in the duodenum and 24% in the esophagus. A histological analysis of the livers of four EGF treated and four non-EGF treated mice was done, but no consistent differences in terms of necrosis, inflammation or regeneration were observed between the two groups.

Key Words:

• Thioacetamide
• circadian
• intestinal tract
• mice
• spleen
• bone marrow
• thymus
• liver
• cornea
• mitosis
• DNA synthesis