The nongenotoxic carcinogens phenobarbitone (PB) and methyl clofenapate (MCP) and the hepatomitogen pregnenolone 16α carbonitrile (PCN) are direct inducers of hepatic S -phase in rats, whereas the S -phase seen after partial hepatectomy is regenerative. We have investigated S -phase and immediate-early gene expression (c-myc and c-jun) in rat liver following these treatments to study the differences in gene expression associated with direct vs. regenerative responses. Both partial hepatectomy (one- and two-thirds) and mitogen treatment caused an increase in hepatic S -phase that peaked around 36 hours. Two-thirds partial hepatectomy caused the greatest increase in S -phase followed by one-third partial hepatectomy, then the mitogens PCN, MCP, and PB in that order. This order of response was also seen with c-jun and to a lesser degree with c-myc expression, suggesting that immediate-early gene expression might be linked not only to regenerative S -phase but also to direct mitogen-induced responses. © 1997 John Wiley & Sons, Inc. J Biochem Toxicol 12: 79–82, 1998

Liver Regeneration

Inducer

10.1002/(sici)1099-0461(1998)12:2<79::aid-jbt2>3.3.co;2-s

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Citations (1)

Hepatic peroxisome proliferation in rodents and its significance for humans

Food and Chemical Toxicology (1993)

P. Bentley I. C. Calder Cliff Elcombe P. Grasso D.A. Stringer

Organelle

10.1016/0278-6915(93)90225-n

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Citations (273)

Species Difference in Hepatic Peroxisome Proliferation

Human Toxicology (1985)

Angela M. Mitchell Kevin Joseph Cliff Elcombe

Peroxisome proliferator

10.1177/096032718500400541

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Citations (7)

Increased hydroxyl radical production in liver peroxisomal fractions from rats treated with peroxisome proliferators

Carcinogenesis (1986)

B.M. Elliott Natalie Dodd Cliff Elcombe

Journal Article Increased hydroxyl radical production in liver peroxisomal fractions from rats treated with peroxisome proliferators Get access B.M. Elliott, B.M. Elliott Search for other works by this author on: Oxford Academic PubMed Google Scholar N.J.F. Dodd, N.J.F. Dodd 1Paterson Laboratories, Christie Hospital and Holt Radium InstituteWilmslow Rd, Withington, Manchester M20 9BX, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar C.R. Elcombe C.R. Elcombe Search for other works by this author on: Oxford Academic PubMed Google Scholar Carcinogenesis, Volume 7, Issue 5, May 1986, Pages 795–799, https://doi.org/10.1093/carcin/7.5.795 Published: 01 May 1986 Article history Received: 03 October 1985 Accepted: 07 February 1986 Published: 01 May 1986

Clofibrate

Hydroxyl radical

10.1093/carcin/7.5.795

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Citations (87)

Biomarkers and molecular tumour classification for non-genotoxic carcinogenesis

Toxicology Letters (2009)

Jonathan G. Moggs C. Roland Wolf Thomas Friedberg Neil A. Stewart Cliff Elcombe

Ouchterlony double immunodiffusion

Immunodiffusion

Provirus

10.1016/j.toxlet.2009.06.722

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Citations (0)

Cruciferous vegetables and drug-metabolising enzyme phenotype

Toxicology (2000)

Carol Murray Barbara M. Elcombe Matthew Harrison Alun Barton ANGUS D. REID

Cruciferous vegetables

10.1016/s0300-483x(00)90304-4

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Citations (0)

A cytological comparison between regeneration, hyperplasia and early neoplasia in the rat liver

Carcinogenesis (1987)

J.A. Styles M.D. Kelly Cliff Elcombe

Regeneration, hyperplasia and neoplasia are three different responses to injury in the rat liver. These phenomena were induced in rat liver and the parameters of ploidy, nuclearity and DNA synthesis were examined. Analysis of hepatocytes from animals undergoing liver regeneration following two-thirds partial hepatectomy revealed that there is an increase in the cycling of diploid hepatocytes and a large increase in the frequency of binucleated tetraploid cells undergoing DNA synthesis and amnitotic cytokinesis to mononucleated tetraploid cells. This results in an overall increase in the ratio of tetra ploid:diploid cells but no change in the proportion of binucleated cells. The liver appears, temporarily, to undergo an increased rate of maturation. In both hyperplasia induc ed by oral administration of 25 mg/kg methylclofenapate or diethylhexylphthalate (1 g/kg for 4 weeks) and neoplasia in duced by the hepatocarcinogens 3′-methyl-4-dimnethylamino-azobenzene (3′M), 6-p-dimethylaminophenylazobenzthiazole (6BT), 5-phenylazoindazole (5I), diethylnitrosamine (DEN) and thioacetamide (TA) the binucleated cell is sensitive to the action of the chemicals, although its response is different. Both types of carcinogen induce a reduction in the frequency of binucleated cells but the mononucleated diploid cells produced by cytokinesis without a preceding S phase as a result of the action of genotoxic carcinogens appear to be incapable of poly-ploidization and give rise to a liver with a pennanently depressed tetraploid:diploid hepatocyte ratio. The non-genotoxic carcinogens methyiclofenapate and DEHP cause an initial hyperplastic response due to the rapid conversion of binucleated cells to mononucleated tetraploids by amitotic cytokinesis following S phase. Over a longer period of ex posure there is an increase in the tetraploid:diploid ratio due to the continued conversion of newly formed binucleates to tetraploid mononucleates.

Binucleated cells

Methylnitronitrosoguanidine

Liver Regeneration

Thioacetamide

10.1093/carcin/8.3.391

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Citations (48)

Measurement of Substrate-induced Oxygen Uptake during Microsomal Drug Oxidation using a Gold Micro-electrode

Xenobiotica (1975)

C. R. Wolf Cliff Elcombe H. Paul A. Illing James Winfred Bridges R. H. Nimmo‐Smith

1. A resin-coated gold micro-electrode has been used for polarographic determination of oxygen concentration in liver microsomal suspensions from phenobarbital-pretreated rats.2. The rate of oxygen uptake on addition of an NADPH-regenerating system and the rate after addition of various substrates of the mixed function oxidase system were measured. The rate of oxygen uptake was faster in the presence of substrate than in the presence of NADPH alone.3. Kinetic constants (Km and Vmax) for biphenyl, hexobarbital, ethylmorphine, naphthalene and SKF 525-A measured by this technique compare favourably with those obtained either by measurements of NADPH oxidation, or chemical measurements of substrate disappearance or product formation.4. The practical applications of the gold electrode to drug metabolism studies are discussed.

Ethylmorphine

Hexobarbital

Clark electrode

Polarography

10.3109/00498257509056103

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Citations (8)