ABSTRACT
The study of immune response and inflammation gene polymorphisms in a genogeographic context is relevant in the study of human populations. Here, in the indigenous populations of Siberia the frequencies of polymorphic variants -174G/C (rs1800795) and -572C/G (rs1800796) of the IL6 gene encoding the proinflammatory cytokine IL-6 were determined. For the first time, it was shown that the frequencies of the -174G and -572C alleles, which determine increased inflammatory response and are also associated with several diseases were statistically significantly higher in ethnic groups of Buryats, Teleuts, Yakuts, Dolgans and Tuvinians than in Russians living in Siberia. These values were in the intermediate position between those in the European and East-Asian groups. We hypothesize an adaptive role of these IL6 genetic variants in human settlement from Africa to the Eurasian continent. However, due to the departure from the traditional way of life and the increasing anthropogenic environmental pollution, the risk of diseases whose pathogenesis is based on inflammation in indigenous Siberian populations is likely increased.
Subject(s)
Indigenous Peoples , Interleukin-6 , Humans , Alleles , Gene Frequency , Indigenous Peoples/genetics , Inflammation , Interleukin-6/genetics , Polymorphism, Single Nucleotide , SiberiaABSTRACT
Sanfilippo syndrome (mucopolysaccharidosis type III) is a lysosomal disorder caused by a defect in the catabolism of heparan sulfate. Mucopolysaccharidosis type III is the most common type of all mucopolysaccharidoses. The pathogenic basis of the disease consists of the storage of undegraded substrate in the central nervous system. Progressive cognitive decline resulting in dementia and behavioural abnormalities are the main clinical characteristics of Sanfilippo syndrome. Mucopolysaccharidosis type III may be misdiagnosed as otherforms of developmental delay, attention deficit/hyperactivity disorder and autistic spectrum disorders because of lack of somatic symptoms, presence of mild and atypical forms of the disease. Patients with Sanfilippo syndrome may have comparatively low urinary glycosaminoglycans levels resulting in false negative urinary assay. Definitive diagnosis is made by enzyme assay on leucocytes and cultured fibroblasts. There is currently no effective treatment of mucopolysaccharidosis type III, though ongoing researches of gene, substrate reduction and intrathecal enzyme replacement therapies expect getting curative method to alter devasting damage of central nervous system in near future.
Subject(s)
Genetic Predisposition to Disease , Mucopolysaccharidosis III , Fibroblasts/pathology , Global Health , Humans , Morbidity/trends , Mucopolysaccharidosis III/diagnosis , Mucopolysaccharidosis III/epidemiology , Mucopolysaccharidosis III/geneticsABSTRACT
Abstract-The study of immune response and inflammation gene polymorphisms in a genogeographic context is relevant in the study of human populations. Here, in the indigenous populations of Siberia the frequencies of polymorphic variants â174G/C (rs1800795) and â572C/G (rs1800796) of the IL6 gene encoding the proinflammatory cytokine IL-6 were determined. For the first time, it was shown that the frequencies of the â174G and â572C alleles, which determine increased inflammatory response and are also associated with several diseases were statistically significantly higher in ethnic groups of Buryats, Teleuts, Yakuts, Dolgans and Tuvinians than in Russians living in Siberia. These values were in the intermediate position between those in the European and East-Asian groups. We hypothesize an adaptive role of these IL6 genetic variants in human settlement from Africa to the Eurasian continent. However, due to the departure from the traditional way of life and the increasing anthropogenic environmental pollution, the risk of diseases whose pathogenesis is based on inflammation in indigenous Siberian populations is likely increased.
ABSTRACT
Genetic and demographic characteristics of populations from two settlements from the Aginskii Buryat district of Trans-Baikal krai (Alkhanai and Orlovskii) were studied. It was demonstrated that the mononational Buryat settlement of Alkhanai, located in the agrarian Dul'durginskii region of the district far from large settlements and transport highways, is characterized by a large prereproductive volume (45%) and by a small share of individuals from the elderly age group (16.4%). A shift in age characteristics in the Buryat group (36.6 and 22.4%, respectively) was detected in the urban settlement of Orlovskii with a population of mixed ethnic composition, located in a densely populated industrialized part of the district. A modified sex ratio was also demonstrated in Alkhanai as opposed to the Buryat part of the Orlovskii population (sex indices were 0.94 and 0.99). Analysis of population mixture was conducted; marriage structure and migrations were described. The endogamy index of the Alkhanai locality was 0.41; in the group of Buryats from Orlovskii, 0.09. A decrease in the amount of pregnancies and births and a larger distribution of family planning practice among Buryats from Orlovskii were detected. The average amount of births of living children per woman in Alkhanai was 5.11; in Buryats from Orlovskii, 3.90. The selection pressure was estimated as low by means of the Crow index (I(tot) 0.28-0.48). In all described groups, a component that characterizes differential fertility (I(f)) exceeds the child mortality component (I(m)).
Subject(s)
Adaptation, Physiological/genetics , Demography , Ethnicity/genetics , Genetics, Population , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Child , Child, Preschool , Family Characteristics , Female , Humans , Male , Marriage , Polymorphism, Genetic , Russia/epidemiology , Sex CharacteristicsABSTRACT
Investigation of the frequencies of functionally signif icant gene variants in the context of medical biology and gene geography is a relevant issue for studying the genetic structure of human populations. The transition from a traditional to an urbanized lifestyle leads to a higher incidence of civilizational diseases associated with metabolic disorders, including type 2 diabetes mellitus. The goal of the present paper is to analyze the frequencies of functionally signif icant gene alleles in the metabolic prof iles of indigenous Siberian peoples to identify the gene pool resilience, evaluate the susceptibility of various ethnic groups to metabolic disorders under changing environmental conditions, and predict the epidemiological situation that may occur in the near future. The study was performed in the monoethnic samples of eastern and western Buryats, Teleuts, Dolgans, and two territorial groups of Yakuts. A real-time PCR was used to determine the frequencies of single nucleotide polymorphisms (SNPs) G103894T, rs12255372, and C53341T, rs7903146 in the TCF7L2 gene. The results obtained were compared to the frequencies identif ied for Russians from Eastern Siberia and the values available in the literature. The frequencies of the polymorphic variants studied in the samples from the indigenous Siberian peoples place them in between Caucasian and East Asian populations, following the geographic gradient of polymorphism distribution. A signif icantly lower occurrence of type 2 diabetes risk alleles TCF7L2 (103894T) and TCF7L2 (53341T) in the samples of indigenous Siberian peoples compared to Russians was observed, which agrees with their lower susceptibility to metabolic disorders compared to the newcomer Caucasian population. Taking into account urbanization, a reduced growth in type 2 diabetes incidence may be predicted in indigenous Siberian peoples, i. e. Buryats, Yakuts, Dolgans, and Teleuts, compared to the newcomer Caucasian population. A further study of population structure with respect to different metabolic prof ile genes is required to better understand the molecular genetic foundations of the adaptive potential of indigenous Siberian peoples.
ABSTRACT
To search for new targets of therapy, it is necessary to reconstruct the gene network of the disease, and identify the interaction of genes, proteins, and drug compounds. Using the online bioinformatics tools we have analyzed the current data set related to the metabolism of xenobiotics, mediated by the N-acetyltransferase 2 (NAT2) gene. The study of allelic polymorphism of the NAT2 gene has a prognostic value, allowing to determine the risk of a number of oncological diseases, the degree of increased risk due to smoking and exposure to chemical carcinogens, including drugs. The aim of this study was to determine the frequencies of two important "slow" variants of the NAT2 gene (NAT2*5, rs1801280 and NAT2*7, rs1799931), which significantly affected the rate of xenobiotic acetylation among the indigenous Nenets population of Northern Siberia. The obtained frequencies of polymorphic variants among the Nenets occupy an intermediate value between those for Europeans and Asians, which might indicate specific features of adaptation. We present a model of the distribution of two polymorphic variants of the NAT2 gene involved in the biotransformation of xenobiotics to study the characteristics of their metabolism in the indigenous inhabitants of Yamal.
Subject(s)
Arylamine N-Acetyltransferase , Acetylation , Alleles , Arylamine N-Acetyltransferase/genetics , Arylamine N-Acetyltransferase/metabolism , Gene Regulatory Networks , Humans , Polymorphism, GeneticABSTRACT
UNLABELLED: The purpose of this work was to determine occurrence of serological markers of hepatites B and to describe subtypes of a superficial antigen and genotypes of hepatitis B virus (HBV) isolates among indigenous population of Yamal-Nenets Autonomous Region (YNAR), Russia. METHODS: We investigated 657 serum samples from inhabitants of Shuryskarsky area of YNAR. ELISA method was used to define the hepatitis B markers: HBsAg, anti-HBs (total) and anti-HBc (IgG and IgM). The HBsAg-positive samples were PCR-tested for the presence of HBV DNA. Genotyping of isolates was by sequencing of the Pre-Sl/Pre-82/S region of HBV genome and phylogenetic analysis. Definition of HBsAg subtypes was executed by two methods: ELISA with subtype-specific monoclonal antibodies and S-gene nucleotide sequence analysis. RESULTS: The following occurrence of hepatitis B markers was observed: HBsAg - 3.2%, anti-HBs (total) - 36.2%, anti-HBc IgG - 30.3%, anti-HBc IgM - 1.6%. Frequency of carrying even one of the markers in the observed population was 47.5%. HBV DNA was found in 17 HBsAg-positive samples. Pre-SI, Pre-S2 and S regions sequences were determined for all HBV DNA-positive samples. The phylogenetic analysis showed an accessory of all investigated HBV isolates to genotype D. HBsAg subtypes distribution appeared the following: ayw2 - 23.5%, ayw3 - 70.6%, adw2 - 5.9%. Results of definition of the subtype ELISA method and by the analysis of S gene nucleotide sequences have coincided in 10/11 (90.1%) cases. CONCLUSIONS: The indigenous population of Shuryskarsky area of YNAR belongs to groups with average HBV carrying. Absolute domination of genotype D (subtypes ayw2, ayw3 and adw2) was revealed. High percentage of concurrence of HBsAg subtypes detected by the ELISA method and method of the analysis of S gene primary structure (90%) was observed. Sequencing of HBV S-gene is preferable to define HBsAg subtypes.
Subject(s)
Genetic Variation , Hepatitis B Surface Antigens/genetics , Hepatitis B virus/genetics , Adolescent , Adult , Aged , Enzyme-Linked Immunosorbent Assay , Female , Hepatitis B/microbiology , Humans , Male , Middle Aged , Phylogeny , Seroepidemiologic Studies , SiberiaABSTRACT
The marriage structure of Nganasans during the time period from 1796 to 1991 and genealogy of carriers of mitochondrial DNA haplotypes was studied in a sample of 280 individuals. It was shown that, from the beginning of its formation to the late 1970s, the population exhibited high endogamy (1976, 83.8%; 1926, 88.4%; 1976, 74.3%). The main source of traditional marriage migration (preferentially female) was populations of Entsy and, indirectly, Nentsy. Intense assimilation of Nganasans by the immigrant population, and to a lesser extent, by Dolgans, in the second half of the 20th century resulted in a reduction of endogamy index in Avam Nganasans to 42.5% by 1991. Assimilation by the immigrants was predominantly paternal, promoting preservation of the historically formed genetic diversity of the Nganasan mitochondrial gene pool. Genealogical analysis of mtDNA haplotypes showed that a relatively high total frequency of Western Eurasian mtDNA haplogroups (20.4%) in the Mongoloid (according to anthropological type) Nganasan population is explained not only by the common ethnic origin with Entsy and Nentsy, but also by direct marriage migration from the Entsy population and indirect marriage migration, from the Nentsy population. This migration led to accumulation of Entsy-Nentsy maternal lineages in the genealogy of Avam Nganasans (38.9% of the total number). Of all mtDNA haplotypes, 28.6% were introduced to Avam Nganasans by female Entsy and Nentsy, whereas the total frequency of these haplotypes was 0.204. Genetic diversity of mitochondrial DNA haplotypes was 0.935.
Subject(s)
DNA, Mitochondrial/genetics , Genetics, Population , Marriage/ethnology , Population Dynamics/trends , Female , Genetic Markers/genetics , Haplotypes , Humans , Male , Marriage/trends , Pedigree , Rural Population/trends , Russia , SiberiaABSTRACT
The purpose of this study was to establish the frequencies of CYP2D6, CYP1A1, GSTM1 and p53 polymorphic genotypes in Tundra Nentsi, which comprises the small group of indigenous people belonging to Northern Mongoloids and Caucasians of Western Siberia. A total number of 102 Tundra Nentsi individuals and 96 Caucasians of Western Siberia were genotyped by means of polymerase chain reaction-based assays. Mutated alleles comprising CYP2D6*4, CYP1A1Val, GSTM1*0 and p53Pro were analysed along with the wild-type alleles. The results showed the intermedial position of CYP2D6*4 allele frequency in Tundra Nentsi, compared to Caucasians and Orientals (0.07 versus 0.2, P = 0.0003; 0.07 versus 0.003, P = 1 x 10(-6), respectively). Thus, our data indicate that the intermedial position of Tundra Nentsi between Orientals and Caucasians most likely shows the Caucasian ancestral origin of CYP2D6*4 allele. Comparative analysis of p53Pro allele frequency showed the pronounced ethnic differences with geographic gradient. Though the frequency of p53Pro allele ranged from 0.17 in Tundra Nentsi up to 0.3 in Caucasians of Western Siberia (P = 0.002), which is in agreement with the previously reported radial distribution of the known genetic markers. No differences were found in the CYP1A1Val allele distribution among Caucasians of Western Siberia and Caucasoid populations presented in other studies, whereas the frequency of Val allele in Nentsi was 1.5-fold higher (P = 0.076) compared to the Japanese group. It was found that the frequency of GSTM1 null genotype in Tundra Nentsi was only 39.8%. The frequency of GSTM1 null genotype in females was higher than in males (0.27 and 0.50, respectively) but that difference was not statistically significant. Comparative analyses of the distribution of putative markers towards cancer susceptibility, CYP1A1Val, GSTM1*0 and p53Pro alleles, have shown that the healthy Tundra Nentsi population (Northern Mongoloids) have a low number of p53Pro alleles and GSTM1*0/*0 genotypes and a high level of CYP1A1Val alleles. Further investigations of gene polymorphisms in isolated Northern native populations would be valuable in clarifying the origin of Northern natives. All this is important for comparative analyses of pharmacogenetic data in Mongoloid populations.
Subject(s)
Cytochrome P-450 CYP1A1/genetics , Cytochrome P-450 CYP2D6/genetics , Ethnicity , Glutathione Transferase/genetics , Polymorphism, Genetic , Adolescent , Adult , Aged , Base Sequence , Child , DNA Primers , Female , Gene Frequency , Humans , Male , Middle Aged , SiberiaABSTRACT
The present study investigates the molecular basis of the G3m polymorphism expressed by the heavy constant domains of human immunoglobulins gamma 3 chains. By using a new protocol allowing the specific cloning of IGHG3 genes, a total of 51 full-length IGHG3 genomic sequences (about 2 kb) isolated from African, Siberian, West Asian and European population samples were sequenced. IGHG3 sequences were assigned precise G3m haplotypes on the basis of specific associations between G3m allotypes and IGHG3 RFLPs. Specific DNA substitutions involved in the expression of G3m(5), G3m(6), G3m(15), G3m(16), G3m(21), G3m(24) and G3m(28) allotypes were then deduced, elucidating almost completely the determination of the G3m polymorphism at the DNA level. The molecular evolution of G3m haplotypes was investigated by a maximum likelihood phylogeny of IGHG3 sequences. Sequence clusters are shown to be G3m haplotype-specific, corroborating the Gm molecular model deduced from serology, and showing that populations differentiation is much more recent than G3m haplotypes differentiation. The widely distributed G3m(5,10,11,13,14) haplotype is likely to be ancestral to the other G3m haplotypes presently found at high frequencies in different continental areas.
Subject(s)
Alleles , Haplotypes/genetics , Immunoglobulin gamma-Chains/genetics , Polymorphism, Genetic/genetics , Asia, Western , Base Sequence , Ethnicity/genetics , Europe , Female , Gene Frequency , Humans , Male , Phylogeny , Polymorphism, Restriction Fragment Length , Senegal , SiberiaABSTRACT
The purpose of this study was to analyze the relationships between brain hemisphere predominance and disturbance of lipid metabolism in atherosclerosis in different ethnic groups. Three groups of subjects were examined: 52 healthy Selkups (the isolated ethnic population of the Far North), 50 healthy Russian men, living in Novosibirsk, and 78 Russian men, living in Novosibirsk, who had myocardial infarction before the age of 50. Blood cholesterol, low density lypoprotein (LDL) and high density lypoprotein (HDL) levels of the subjects with different brain functional asymmetry were compared. The lack of either hemisphere predominance is the most common among the Selkups. The population of Selkups as a whole showed low concentrations of cholesterol and LDL in comparison with both Russian groups. For all examined groups the pattern of lipid metabolism has been worsened for the subjects showing the left hemisphere predominance. The changes of lipid metabolism indices in subjects with the dominant left hemisphere is discussed.
Subject(s)
Arteriosclerosis/metabolism , Brain/physiology , Lipid Metabolism , Myocardial Infarction/metabolism , Arctic Regions/epidemiology , Arteriosclerosis/complications , Arteriosclerosis/ethnology , Brain/anatomy & histology , Incidence , Myocardial Infarction/ethnology , Myocardial Infarction/etiology , Risk Factors , Russia/epidemiologyABSTRACT
Using mtDNA and classical markers, previous studies have found that the Altai are genetically divergent from the rest of Siberia. This study uses five variable number tandem repeat (VNTR) loci to examine the relationship of the Altai to other indigenous Siberian populations. Frequencies of VNTR fragments have been obtained from the DNA of 95 individuals living in the Altai village of Mendur-Sokkon. A Kolmogorov-Smirnov test shows that the Altai are significantly different from the Evenki village of Surinda at loci D11S129 and D20S15. In addition, the Altai are also statistically different from the Evenki village of Poligus at locus D11S129. The test reveals no differences between the Ket village of Sulamai and Mendur-Sokkon. The GST value obtained for Siberia is significant and is almost equal to that found for the GST of American ethnic groups. The significance of the GST values was verified through random resampling of the data. The GST value is an effect of the relative isolation of the Evenki as well as gene flow into the Kets and Altai; this is shown in a plot of rn versus mean heterozygosity. Although genetic differentiation between the Siberian groups is significant, an R matrix analysis, which uses American and Siberian ethnic groups, shows that the Siberians form a tight cluster. When the R matrix, GST , and the Kolmogorov-Smirnov results are combined, the Altai appear to be genetically different among Siberian populations, yet they are not as genetically divergent as previous studies have shown. © 1996 Wiley-Liss, Inc.
ABSTRACT
Sensitivity of hepatocytes to the proliferative stimulus (partial hepatectomy) and mitoinhibitory effect of carcinogen (toxic dose after operation) was studied during hepatic carcinogenesis induced by the chronic administration of diethylnitrosamine. At early stages of hepatocarcinogenesis (4-6 weeks of carcinogen treatment) in the rat liver tissue there appears and then increases a subpopulation of hepatocytes insensible to proliferation mediators. The cell number in this subpopulation essentially increased in the period preceding the development of microscopically detected neoplastic nodules.
Subject(s)
Diethylnitrosamine/toxicity , Liver Neoplasms/pathology , Liver/drug effects , Nitrosamines/toxicity , Animals , Cell Division/drug effects , Hepatectomy , Liver/pathology , Liver Neoplasms/chemically induced , Liver Regeneration/drug effects , Male , Rats , Rats, Inbred F344ABSTRACT
Different aspects of the interaction of polypeptide growth factors with their receptors are reviewed. The problem of structural and functional interactions of the normal and transforming growth factors as well as the protein products of oncogenes during transmittance of a mitogenic signal and the proliferation regulation of normal and tumour cells is discussed.
Subject(s)
Cell Transformation, Neoplastic/drug effects , Growth Substances/pharmacology , Oncogenes/drug effects , Animals , Cell Transformation, Viral/drug effects , Cells, Cultured , DNA, Neoplasm/genetics , DNA, Viral/genetics , Drug Interactions , Epidermal Growth Factor/pharmacology , Gene Expression Regulation/drug effects , Genes, Viral/drug effects , Male , Mice , Oncogenic Viruses/genetics , Oncogenic Viruses/pathogenicity , Peptides/pharmacology , Platelet-Derived Growth Factor/pharmacology , Protein Biosynthesis/drug effects , Receptors, Cell Surface/drug effects , Transforming Growth Factors , Translocation, Genetic/drug effectsABSTRACT
Proliferative kinetics of hepatocytes and nonparenchymal cells of the regenerating rat liver has been studied after a single injection of the carcinogen in S- or G2-M-phase cell cycle of hepatocytes. Disturbances of proliferation in the mentioned cell populations and resistance of normal proliferating hepatocytes during the S-phase of the mitotic cycle to the cytotoxic effect of the carcinogen are established. Possible mechanisms of the resistance of the proliferating cells to the toxic action of the carcinogen are discussed.
Subject(s)
Diethylnitrosamine/toxicity , Liver Regeneration/drug effects , Animals , Cell Cycle/drug effects , Cell Division/drug effects , Hydroxyurea/pharmacology , Interphase/drug effects , Liver/cytology , Liver/drug effects , Male , Microsomes, Liver/drug effects , Microsomes, Liver/enzymology , Mitosis/drug effects , Oxidoreductases, N-Demethylating/metabolism , Rats , Time FactorsABSTRACT
Hepatocytes in cell culture have been studied for their sensitivity to mitogenic effect of the epidermal growth factor, epidermal growth factor and insulin, 10% of cattle blood serum after hyperthermia. It is established that heat shock (43 degrees C, 90 min) induces hypersensitivity of hepatocytes to the mentioned mitogens, its maximum being observed 20-24 h after hyperthermia and coinciding in time with the development of thermotolerance and intensification of protein biosynthesis after the heat shock 68, 70, 94 kD.
Subject(s)
Heat-Shock Proteins/biosynthesis , Hyperthermia, Induced , Liver/cytology , Animals , Cell Division , Cells, Cultured , Epidermal Growth Factor/pharmacology , Insulin/pharmacology , Male , Mitogens/pharmacology , Rats , Time FactorsABSTRACT
The first step in the isolation of murine epidermal growth factor (EGF) from submaxillary glands was the trace enrichment of the acid-ethanol extract on Sep-pak C18 cartridges using the step elution with ethanol. The fraction eluted by 60% ethanol contained above 75% of EGF. The final purification of EGF was achieved by reverse-phase liquid chromatography on Novapak C18 column in the gradient of acetonitrile. A comparison of the effectiveness of gel filtration (on Bio-gel P-60 column) and trace enrichment (on Sep-pak C18 cartridges) of the appropriate fractions were analyzed by the reverse-phase high-pressure liquid chromatography, which had demonstrated that hydrophobic separation of EGF had a number of advantages. The homogeneous character of EGF was confirmed by the silver staining of gels after disc-electrophoresis and isoelectric focusing (pI 4.8). The pronounced mitogenic effect of EGF on the primary culture of the rat hepatocytes is described.
Subject(s)
Chromatography, High Pressure Liquid/methods , Epidermal Growth Factor/isolation & purification , Animals , Chromatography, Gel , Electrophoresis, Polyacrylamide Gel , Isoelectric Focusing , Male , Mice , Submandibular Gland/analysisABSTRACT
The radioimmunological and radioreceptor methods have been used to show that sialadenectomy leads to the stable decrease of the epidermal growth factor (EGF) concentration in saliva and blood serum. The mean number of colon tumours per rat was significantly lower among the rats which had been sialadenectomized before injections of the carcinogen, than in the control. But a sharp stimulation of carcinogenesis in the duodenal mucosa was observed after sialadenectomy. The production of the alpha-transforming growth factor with the EGF-competing activity for the EGF-receptors was found in the chemically-induced rat colon tumours.
Subject(s)
Epidermal Growth Factor/metabolism , Intestinal Mucosa/metabolism , Intestinal Neoplasms/chemically induced , 1,2-Dimethylhydrazine , Adenocarcinoma/chemically induced , Adenocarcinoma/pathology , Adenocarcinoma/physiopathology , Animals , Dimethylhydrazines , Epidermal Growth Factor/isolation & purification , Intestinal Neoplasms/metabolism , Intestinal Neoplasms/physiopathology , Male , Peptides/isolation & purification , Peptides/metabolism , Rats , Submandibular Gland/metabolism , Transforming Growth FactorsABSTRACT
It is established that sialadenectomy leads to inhibition of hepatocarcinogenesis induced in adult rats by diethylnitrosamine, which is confirmed by a decrease in the incidence of tumours, their delayed growth and an increase of longevity. But sialadenectomy 2 weeks after the beginning of carcinogen treatment has no effect on the hepatocarcinogenesis. A significant molecular heterogeneity of the epidermal growth factor-competing activity is observed in acid-ethanol extracts of the liver tumour of the sialadenectomized rats.
Subject(s)
Diethylnitrosamine/toxicity , Liver Neoplasms, Experimental/chemically induced , Salivary Glands/physiology , Animals , Epidermal Growth Factor/analysis , Epidermal Growth Factor/deficiency , Liver/analysis , Liver Neoplasms, Experimental/analysis , Male , Rats , Salivary Glands/analysis , Salivary Glands/surgery , Time FactorsABSTRACT
The frequency of tumour incidence in rats subjected to the single action of diethylnitrosamine to regenerating liver cells synchronized in different phases of the mitotic cycle was maximal in rats exposed to carcinogen when 62.5% of regenerating liver hepatocytes were in the S-phase. Dietary added phenobarbital increased the number and size of hepatocarcinomas especially in rats which received DENA in the G2-M phase of hepatocytes or during maximal proliferation of nonparenchymal cells. The role of proliferation of different cell populations in initiation and promotion of carcinogenesis is discussed.