Stimulation of hepatocellular proliferation by a serum factor from thioacetamide-treated rats

Morley, Colin G.D.; Boyer, James L.

doi:10.1016/0005-2787(77)90232-5

Cited by 38 publications

(13 citation statements)

References 15 publications

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“…Although the molecular mechanisms that cause these toxic effects in different organs are not understood, TAA is known to interfere with ribosomal activity, thus hindering protein synthesis [11]. TAA administration has also been shown to stimulate DNA synthesis [12]. The current investigation presents an understanding of mechanism of the steatohepatitis disease using zebrafish as a simple and effective animal model.…”

Section: Introductionmentioning

confidence: 99%

Thioacetamide induced liver damage in zebrafish embryo as a disease model for steatohepatitis

et al. 2006

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Section: Introductionmentioning

confidence: 99%

Thioacetamide induced liver damage in zebrafish embryo as a disease model for steatohepatitis

et al. 2006

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“…Thioacetamide, a hepatocarcinogen, stimulates DNA synthesis and mitosis in rats (Morley & Boyer, 1977). Carbon tetrachloride, following toxic liver injury, produces synthesis of DNA in non-necrotic areas (Leevy et al, 1959).…”

Section: Discussionmentioning

confidence: 99%

“…In the case of thioacetamide-injected rats, AST and ALT concentration was only checked at 0, 48 and 72h. The apparent maximum (48h) was chosen by analogy with the DMNA experiments and previous results from other authors (Morley & Boyer, 1977).…”

Section: Discussionmentioning

confidence: 99%

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A liver DNA synthesis promoter induced in rat plasma by injection of dimethylnitrosamine (DMNA) or thioacetamide

Díaz-Gil¹,

Sánchez²,

Santamarı́a³

et al. 1987

Br J Cancer

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Summary The appearance of a liver DNA synthesis promoter (HP) in rat plasma after dimethylnitrosamine (DMNA) or thioacetamide injection was investigated. After 48 h, DMNA (30mg kg-1 body weight) produced liver (centrilobular) necrosis and intense hepatic regeneration, as assessed by microscopic observations of liver slices, as well as augmented transaminase levels; HP was detectable under these conditions. After 5 days, transaminases and HP returned to normal values (the latter undetectable), coinciding with a lack of necrotic zones. At 60mg DMNA kg-' body weight, necrotic areas were more marked and transaminases and HP levels higher after 48 h than with the lower dose; these increases were even more pronounced at 90mg DMNA kg-1 body weight.After thioacetamide injection (200mgkg-1 body wt) the situation at 48h was very similar, with focal, centrilobular necrosis, frequent regenerative signs, high transaminases and detectable HP. Rats recovered after 7 days in a similar fashion as with DMNA. At 400mg thioacetamide kg-1 body weight, necrotic areas and regeneration zones were more widespread and transaminases and HP higher after 48h than with the lower dose.On account of the differing modes of action of DMNA and thioacetamide in rat liver, it is proposed that the appearance of HP activity in plasma could be related to the regenerative process that follows hepatotoxic damage.

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“…Accordingly, it was reported that the hepatotoxic effects ofTA are manifested only after metabolic conversion to thioacetamide-S-oxide, which undergoes further oxidative metabolism to an as yet unidentified toxic metabolite (7). TA has been reported to stimulate DNA synthesis and mitosis in the liver of rats at doses that produce limited necrosis (9)(10)(11). The rise in DNA synthesis induced by TA has been shown to follow a time course that is similar to that seen following partial hepatectomy (12).…”

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Effect of an antimitotic agent colchicine on thioacetamide hepatotoxicity.

Mangipudy

Rao

Mehendale

1996

Environ Health Perspect

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In an earlier study we established that timely and adequate tissue repair response following the administration of a six-fold dose-range of thioacetamide (TA; 50, 150, and 300 mg/kg) prevented progression of injury and led to recovery and animal survival. Delayed and attenuated repair response after the 600 mg/kg TA dose resulted in a marked progression of injury and 100% lethality. The objective of the present study was to further scrutinize this concept in an experimental protocol in which we hypothesized that a selective ablation of the tissue repair response should lead to lethality from the nonlethal, moderately toxic doses of 150 and 300 mg/kg TA. In this study we investigated the effect of the antimitotic agent colchicine (CLC, 1 mg/kg) on the outcome of TA hepatotoxicity. Male Sprague-Dawley rats (175-225 g) were injected intraperitoneally (ip) with 150 and 300 mg/kg TA. We assessed liver injury by serum enzyme elevations and histopathology. Tissue regeneration response was measured by 3H-thymidine incorporation into hepatonuclear DNA and by proliferating cell nuclear antigen (PCNA) assay. S-Phase stimulation, as indicated by 3H-thymidine incorporation, was noted at 36 and 48 hr following the administration of 150 mg/kg TA, whereas with the 300 mg/kg TA S-phase stimulation was elicited at 48 hr following treatment. Therefore, two doses of CLC (30 hr and 42 hr, 1 mg/kg, ip) were administered to the 150 mg/kg treated group while a single dose of CLC (42 hr, 1 mg/kg, ip) was administered to the 300 mg/kg group. CLC treatment resulted in 100% lethality in both groups. Thus, CLC administration converted nonlethal doses into lethal doses. The 150 mg/kg TA dose was then chosen to further investigate the underlying mechanism. Rats treated with TA alone recovered from injury by 36-48 hr while CLC treatment resulted in a progression of injury as indicated by serum enzyme elevation and histopathology. Tissue repair, as evidenced by 3H-thymidine incorporation and PCNA studies explained this dichotomy. Antimitotic intervention with CLC resulted in a significantly diminished repair response leading to unrestrained progression of injury and lethality even from nonlethal doses. This model demonstrates the critical role of tissue repair response in determining the final outcome of toxicity. Images Figure 1. Figure 2. Figure 3. Figure 3. Figure 3. Figure 3. Figure 3. Figure 3. Figure 5. Figure 5. Figure 5. Figure 5. Figure 5. Figure 5. Figure 4. Figure 6.

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Stimulation of hepatocellular proliferation by a serum factor from thioacetamide-treated rats

Cited by 38 publications

References 15 publications

Thioacetamide induced liver damage in zebrafish embryo as a disease model for steatohepatitis

Thioacetamide induced liver damage in zebrafish embryo as a disease model for steatohepatitis

A liver DNA synthesis promoter induced in rat plasma by injection of dimethylnitrosamine (DMNA) or thioacetamide

Effect of an antimitotic agent colchicine on thioacetamide hepatotoxicity.

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