RESUMO
The data on the changes in the isoenzyme spectrum of pepsinogen-pepsin inversely correlating with the development and retaining of the malignant condition of gastric mucosa in human and animals are reviewed. The results of the molecular-genetic studies of gastric carcinogenesis, in particular the role of protooncogenes--oncogenes in this process are presented.
Assuntos
Neoplasias Gástricas/etiologia , Animais , Fenômenos Bioquímicos , Bioquímica , Cães , Mucosa Gástrica/metabolismo , Humanos , Oncogenes , Proto-Oncogenes , Coelhos , Ratos , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismoRESUMO
The dependence of gastrocarcinogenesis on biochemical and morphological disorders of the stomach mucous membrane, i.e. epimolecular alteration of chromatin structure, inhibition of pepsinogen synthesis, alteration of ontogenetic heritage of glandular epithelium was studied in 450 random-bred white rats with the aid of a model of gastrocarcinogenesis induced with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). This agent weakened the DNA-protein linkage in the chromatin. The irreversibility of this phenomenon coincided with the crucial point of the MNNG gastrocarcinogenesis (precancer sign appearance). The consequences of MNNG-induced specific alteration of epithelial stem cells became inherited (stomach adenocarcinoma development). In parallel with gastrocarcinogenesis, concomitant deficiency of pepsinogen-pepsin in the mucous membrane also developed. The data suggest that deficiency of the enzyme was in some degree obliged to alteration of pepsinogen mRNA synthesis.
Assuntos
Adenocarcinoma/induzido quimicamente , Mucosa Gástrica/patologia , Metilnitronitrosoguanidina , Neoplasias Gástricas/induzido quimicamente , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Animais , Cromatina/efeitos dos fármacos , Feminino , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Masculino , Pepsinogênios/biossíntese , RNA Mensageiro/biossíntese , Ratos , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologiaRESUMO
Biochemical changes in the stomach mucous membrane of rats treated with N-methyl-N-nitro-N-nitrosoguanidine (MNNG) were studied. Carcinogenesis was shown to involve considerable changes in gastric mucous membrane, e. g. disorders in biosynthesis of isoforms of pepsinogen-pepsin. Their level and proteolytic activity are gradually declined. This effect can be reversed at an early stage of treatment and is persistent in advanced tumors of glandular part of rat stomach.
Assuntos
Mucosa Gástrica/efeitos dos fármacos , Metilnitronitrosoguanidina/farmacologia , Animais , Feminino , Mucosa Gástrica/metabolismo , Masculino , Neoplasias Experimentais/induzido quimicamente , Neoplasias Experimentais/metabolismo , Pepsina A/metabolismo , Pepsinogênios/metabolismo , Polirribossomos/metabolismo , Ratos , Neoplasias Gástricas/induzido quimicamente , Neoplasias Gástricas/metabolismo , Fatores de TempoRESUMO
An infectious process was reproduced in the culture of chick embryo cells by means of DNA isolated from Rous chick sarcoma tissue (Carr-Zilber strain). This DNA preparation displays biological activity also in the culture of human embryo diploid cells (HEDC) which is manifested in: 1. discontinuous synthesis of avian oncovirus group-specific antigen; 2. enhancement of proliferative activity and morphological transformation of human cells; 3. continuous presence of virus-specific sequences as revealed by DNA/RNA hybridization. Producing complete oncornavirus by means of DNA isolated from Rous chick sarcoma in HEDC was unsuccessful. DNA preparation from gs negative chick embryo cells shows no infectious activity in HEDC culture.