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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this investigation was to determine whether mitogen-induced cell proliferation is as effective as compensatory cell proliferation in achieving initiation of carcinogenesis in rat liver. Male Wistar rats were injected with a single non-necrogenic dose of the hepatocarcinogen diethylnitrosamine (DENA) during the peak of DNA synthesis following the administration of the hepatic mitogen ethylene dibromide (EDB) or a necrogenic dose of CCl4. After subjecting the animals to a promoting procedure, the rats were sacrificed and the initiated hepatocytes were monitored as gamma-glutamyltranspeptidase (gamma-GT) positive foci. The results indicate that while DENA administration during compensatory cell proliferation results in the formation of GT positive foci, no enzyme-altered foci were produced when the carcinogen was given during liver hyperplasia induced by EDB, despite the fact that at the time of carcinogen administration, the extent of cell proliferation, as monitored by thymidine incorporation into DNA, was the same in both the groups.
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PMID:Liver cell proliferation induced by the mitogen ethylene dibromide, unlike compensatory cell proliferation, does not achieve initiation of rat liver carcinogenesis by diethylnitrosamine. 288 28

The effects of dietary vitamin E (VE) on the steps of hepatocarcinogenesis, the induction and growth of gamma-glutamyltranspeptidase (GGT)-positive foci and their evolution into persistent nodules, were analyzed in the liver of rats treated with diethylnitrosamine (DEN). The induction of GGT-positive foci was inhibited by a diet containing 0.36-1.5% VE given after initiation with 200 mg/kg body weight (b.w.) DEN for 6 weeks with partial hepatectomy (PH) on week 3. The numbers and areas of GGT-positive foci were enhanced by diets containing 0.36 and 0.72% VE, given for 1 week after initiation with 10 mg/kg b.w. DEN and PH, followed by selection by 0.02% 2-acetylaminofluorene (AAF) and carbon tetrachloride (CCl4), but these were not enhanced by a diet containing 1.5% VE. Remodeling of hyperplastic nodules was not affected by the diet containing 0.72% VE given after initiation with DEN and selection for 12 weeks. The staining characteristics of GGT were different between remodeling and persistent nodules, except for those of the glutathione-S-transferase placental form (GST-P). The results obtained suggest that VE could prevent the very early events during hepatocarcinogenesis, the induction of phenotypically altered foci, but could no longer affect the later stages, the evolution of foci into persistent nodules.
Carcinogenesis 1987 Nov
PMID:Effect of vitamin E on the induction and evolution of enzyme-altered foci in the liver of rats treated with diethylnitrosamine. 288 37

This study concerns the modifying effect of carbon tetrachloride (CCl4) on methylazoxymethanol acetate (MAM)-induced intestinal carcinogenesis in ACI rats of both sexes. Forty five animals were given CCl4 (0.5 ml/kg body weight) through a stomach tube, followed by an i.p. injection with MAM (25 mg/kg body weight) 24 hours after CCl4 treatment. The paired administrations were done once a week for 4 weeks and animals were observed until sacrifice 30 weeks later. Pretreatment with CCl4 caused not only early death from chemical toxicity of MAM but also an increase in small-bowel tumors.
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PMID:Enhancing effect of preadministration of carbon tetrachloride on methylazoxymethanol acetate-induced intestinal carcinogenesis. 300 71

The expression of RNA transcripts from three families of endogenous retrovirus-related sequences was investigated during liver cell proliferation in B6C3 mice. Treatment with a single dose of the liver mitogen and promoter of mouse hepatocarcinogenesis 1, 4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), or with carbon tetrachloride (CCl4), induced liver cell proliferation at days 2 and 3 after treatment. Both of these treatments led to a marked increase in Moloney murine leukemia virus-related 6 kilobase RNAs, which were most abundant at day 1 after TCPOBOP treatment and at day 2 after CCl4. Intracisternal A particle-related 6 kilobase RNAs were markedly increased at days 1 and 2 after TCPOBOP and at days 1, 2, and 3 after CCl4. VL30-related transcripts were slightly decreased after TCPOBOP, but they were markedly increased at days 1 and 2 following CCl4. The livers of 15-day-old untreated mice contained about a 3-fold higher level of Moloney murine leukemia virus-related RNAs than adult liver. Intracisternal A particle-related 6-kilobase transcripts were present at 3-fold higher abundance in 7-day-old than in 15-day-old or adult liver. RNAs homologous to VL30 were detected at about the same levels in infant as well as adult livers. Inhibition of protein synthesis by the administration of cycloheximide to adult mice caused a marked increase in the amount of Moloney murine leukemia virus-, intracisternal A particle-, and VL30-related RNAs in the livers of the treated mice, suggesting the existence of labile proteins that normally regulate the abundance of these transcripts. We postulate that the amounts of these putative regulatory proteins vary during both normal development and carcinogenesis and also in response to specific agents that induce liver cell proliferation.
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PMID:Factors influencing the expression of endogenous retrovirus-related sequences in the liver of B6C3 mice. 310 24

The effect of the 'promoters' phenobarbital (PB) and butylated hydroxytoluene (BHT) on the ploidy changes during hepatocarcinogenesis in rats was compared in a densitometric analysis of Feulgen-stained nuclei on paraffin-embedded tissue slices. The triphasic Gerlans protocol for liver-cancer induction was applied. Initiation with a single dose of diethylnitrosamine (DEN), and selection with 2-acetylamino-fluorene (2-AAF) combined with a proliferative stimulus (CCl4 administration), was followed by a treatment with PB or BHT for periods up to 22 weeks. Control animals received no treatment after the initiation and selection procedure. Despite intra- and inter-individual variations, an increase in the amount of 2N nuclei is found in the putative preneoplastic lesions of animals that received initiation and selection (I-S) and 3 weeks basal diet (BD). When the diet is supplemented with PB (after I-S), the increase of diploid nuclei starts earlier. At the time carcinoma arise (22 weeks PB treatment) a decrease in the frequency of 2N nuclei is found. BHT-treated animals which develop no carcinoma within the considered timespan, show a clear increased amount of 2N nuclei in the precancerous lesions only after 14 weeks treatment. It seems that there is a positive correlation between the outgrowth of putative preneoplastic foci and nodules in rat liver and an increase of diploid nuclei in these lesions. PB, as promoter used after initiation and selection, speeds up the development of carcinoma in rat liver, and therefore also the shift to diploidization in these rats starts earlier in comparison with I-S-treated rats. Although BHT does not promote liver carcinogenesis, an increase of diploid nuclei is also observed here during lesion formation. It may, therefore, be concluded that the phenomenon of diploidization is closely linked to and probably necessary for preneoplastic development, but that it is not an absolute indicator for neoplastic transformation.
Carcinogenesis 1988 Oct
PMID:The influence of phenobarbital and butylated hydroxytoluene on the ploidy rate in rat hepatocarcinogenesis. 316 55

The effect of phenobarbital (PB), p,p'-dichlorodiphenyltrichloroethane (DDT) or carbon tetrachloride (CCl4) on dimethylnitrosamine (DMN)-induced hepatocarcinogenesis in Syrian golden hamsters was examined. Hamsters were given a single injection of DMN (6 mg/kg body wt) followed by either PB or DDT in the diet or repeated CCl4 gavage for 30 weeks. The numbers of both altered liver cell foci and hepatocellular neoplasms in the hamsters given 0.1 ml CCl4, i.g. once every 2 weeks after the DMN were significantly higher than in the animals given DMN alone. PB or DDT (500 p.p.m. in the diet) after DMN did not produce a significantly higher incidence of altered foci or hepatocellular neoplasms compared to DMN alone. Thus, an enhancing effect of CCl4 on DMN-induced hepatocarcinogenesis in the hamster was demonstrated, but neither PB or DDT--both liver neoplasm promoters in rats and mice--displayed promoting activity under the conditions of study.
Carcinogenesis 1987 Sep
PMID:Enhancement of dimethylnitrosamine-initiated hepatocarcinogenesis in hamsters by subsequent administration of carbon tetrachloride but not phenobarbital or p,p'-dichlorodiphenyltrichloroethane. 330 90

The in vitro covalent binding of 14C-labelled carbon tetrachloride [14C]CCl4 to histones and non-histone chromosomal proteins (NHCP) under microsome-mediated aerobic conditions was determined. Whole chromatin was prepared from purified nuclei isolated from livers of B6C3F1 hybrid mice and incubated with 2.5, 5.0 and 10.0 mumol [14C]CCl4 in the presence of microsomes isolated from the same tissue, at 4 mg protein, and an NADPH-regenerating system at 37 degrees C for varying incubation times. Binding of [14C]CCl4 to histones and NHCP was also determined in the presence of 5 mM L-cysteine. The results show that the activated intermediate of CCl4 bound more to histones than to NHCP in a dose- and time-dependent manner, and that 5 mM L-cysteine inhibited the binding of the activated intermediate of CCl4 to histones by 59%, without affecting the binding to NHCP. These data suggest different extents of alkylation or acylation between histones and NHCP by metabolically activated CCl4 under aerobic in vitro conditions, and differential inhibition of CCl4-alkylation-acylation by cysteine. This suggestion does not exclude other possible mechanisms of action.
Carcinogenesis 1987 Jun
PMID:Time-related binding of the hepatocarcinogen carbon tetrachloride to hepatic chromatin proteins in vitro. 360 85

It was demonstrated that chloroform--studied in the non-toxic concentration interval 0.025-0.1% w/v--as well as carbon tetrachloride at 0.0125-0.05%, can support proliferation of cell cycling human embryonic lung fibroblasts in Dulbecco's modified Eagle's medium (DMEM) complemented with 0.5% foetal calf serum. This serum concentration restricts the growth of the non-solvent treated fibroblast (control) cultures. Even after a pretreatment of the fibroblasts with the low serum-medium for up to 4 days, the cells responded to the mitogenic impulse of the solvents. This indicates that quiescent fibroblasts are also sensitive to the mitosis-stimulating effect of the solvents. The effect of the solvents in serum-free DMEM was followed in a short-term study in order to determine if cofactor(s) from serum are needed for expression of the mitosis-stimulating activity of the solvents. Carbon tetrachloride was shown to be mitogenic for the fibroblasts. At solvent concentrations greater than or equal to 0.00078% w/v the cells were observed to proliferate about as rapidly as control cells incubated in 10% serum-containing DMEM. After change from solvent-containing to solvent-free medium cell proliferation was soon inhibited. Chloroform was not mitogenic in the serum-free medium. The mitogenic activity of CHCl3 or CCl4 in solvent containing 10% serum and reduced content of calcium ions (0.05 mM) was then determined. It was shown that the solvents under the non-physiological conditions support proliferation of the fibroblasts for 2-3 days depending on the solvent concentration.
Carcinogenesis 1987 Nov
PMID:Mitogenic activity of chloroform and carbon tetrachloride in serum-deficient or calcium-deficient cultures of human embryonic lung fibroblasts. 366 56

Two complementary genetic parameters were followed in liver parenchymal cells during the first steps of rat hepatocarcinogenesis: the expression of nucleolar genes estimated from their silver stainability and the nuclear DNA content determined after Feulgen staining. Putative preneoplastic lesions as foci and nodules were induced by the triphasic 'Gerlans protocol'. Initiation with a single dose of diethylnitrosamine (DEN) was followed by a selection of initiated cells with 2-acetylaminofluorene (2-AAF) in combination with a single necrogenic dose of CCl4 as a proliferative stimulus. Finally after 1 week of normal diet, the animals were treated or not with phenobarbital (PB) for periods up to 2 months. Serial sections were analysed after silver staining (AgNO3), methyl-green--pyronin staining (Unna-Brachet) and Feulgen staining with densitometric and morphometric methods. Silver staining, which is known to stain an acidic protein associated with rRNA synthesis, increased gradually with the duration of the PB treatment. Morphometry revealed an increase in both nucleolar and nuclear volume; the fraction of nuclei with one nucleolus also increased. These results seem to point towards an increase of nucleolar activity in the early steps of PB promotion. Moreover, this shift cannot be ascribed to an increase of DNA content. Indeed, a parallel study on neighbouring sections stained with Feulgen revealed a shift towards a population of diploid nuclei, in contrast to normal liver cells, which are mostly tetraploid. The observed diploidisation may therefore provide a functional advantage for the expansion of putative preneoplastic cells.
Carcinogenesis 1987 Feb
PMID:Changes in nucleolar transcriptional activity and nuclear DNA content during the first steps of rat hepatocarcinogenesis. 380

Experiments were designed to determine whether mitogen-induced cell proliferation is as effective as regenerative cell proliferation in achieving initiation of liver carcinogenesis. To test this hypothesis male Wistar rats were injected with a single dose of diethylnitrosamine (DENA) or N-methyl-N-nitrosourea (MNU) during the peak of DNA synthesis following the administration of the liver mitogen, lead nitrate, after partial hepatectomy (PH) or a necrogenic dose of CCl4. The initiated hepatocytes were monitored as gamma-glutamyltransferase (GGT)-positive foci using a 2-week selection regimen consisting of 0.03% 2-acetylaminofluorene (2-AAF) coupled with a necrogenic dose of CCl4. The results indicate that unlike compensatory cell proliferation such as that induced by PH or CCl4, mitogen-induced cell proliferation did not result in any initiated hepatocytes despite the fact that in both types of models the extent of liver cell proliferation at the time of the administration of the carcinogen is similar.
Carcinogenesis 1987 Feb
PMID:Failure of mitogen-induced cell proliferation to achieve initiation of rat liver carcinogenesis. 380 22


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