Assuntos
Antineoplásicos Alquilantes/farmacologia , DNA de Neoplasias/efeitos dos fármacos , RNA de Cadeia Dupla/farmacologia , RNA Fúngico/farmacologia , Sarcoma Experimental/metabolismo , 5-Metilcitosina , Animais , Citosina/análogos & derivados , Citosina/metabolismo , DNA de Neoplasias/metabolismo , Fígado/metabolismo , RatosRESUMO
Methylation and secondary structure of DNA in rat liver versus time of aflatoxin B1 (AfB1) treatment were studied. A 50% drop in 5-methylcytosine level in liver DNA as compared with control was observed long before tumor development. Also, certain changes in DNA secondary structure were seen. The DNA changes were more pronounced in the F1 progeny of rats inoculated with AfB1 at the terminal stage of gestation.
Assuntos
Aflatoxinas/farmacologia , Carcinógenos/farmacologia , DNA/efeitos dos fármacos , Fígado/efeitos dos fármacos , Conformação de Ácido Nucleico/efeitos dos fármacos , Aflatoxina B1 , Animais , Composição de Bases/efeitos dos fármacos , DNA/análise , DNA/metabolismo , Dimetilformamida/farmacologia , Feminino , Fígado/enzimologia , Metilação , Ratos , Ratos Endogâmicos , EspectrofotometriaRESUMO
Secondary structure and the rate of methylation of DNA, isolated from normal and malignant liver tissues (sarcoma 45) were studied in vivo and in vitro in presence of sarcolysine. The differential melting curve (DMC) in the DNA from malignant tissue was shifted, compared with that of the liver DNA, to the low temperature side and was characterized by appearance of an additional peak in the region of 50-60 degrees. A considerable increase in the level of methylation has been also noted in the DNA from malignant tissue. Sarcolysine caused a partial restoration of the DMC patterns and decreased by 20% the content of m5C in vivo; the DMC of the DNA from malignant tissue retained practically all its low-temperature features in vitro. The data obtained suggest that sarcolysine does not act directly on the DNA from malignant tissue but participates in an intermediate process, exhibiting a selective action on DNA.
Assuntos
DNA de Neoplasias/metabolismo , DNA/metabolismo , Melfalan/farmacologia , Conformação de Ácido Nucleico/efeitos dos fármacos , Sarcoma Experimental/metabolismo , Animais , Técnicas In Vitro , Fígado/efeitos dos fármacos , Fígado/metabolismo , Metilação , RatosRESUMO
The content of 5-methyl cytosine (5-MC) in the DNA preparations from organs and tissues of healthy and tumour-bearing (sarcoma 45) rats and the effect of an alkylating cancerolytic agent on DNA methylation in vivo were studied. The 5-MC content in the DNA preparations from liver, spleen and testicles of tumour-bearing rats and tumour cells was increased, the maximal increase being observed in liver and spleen DNAs (1,71 and 1,70 mol.%, respectively) and in sarcoma DNA (1,93 mol.%) on the 8th post-inoculation day. On the 8th and 15th day following daily injections of the cancerolytic agent the 5-MC content in the DNAs from liver and spleen of the control animals was decreased in a number of cases almost down to normal level (1,00 mol.%). Tumour DNA did not differ from normal tissue DNA with respect to Tmelt and GC content; however, its differential melting curve revealed an additional "shoulder" within the temperature range of 56--60 degrees, which was partly removed after addition of the cancerolytic agent. It was assumed that the changes in the methylation level and secondary structure of DNA can be due to the cancerolytic activity of the preparation.