RESUMEN
N-Nitrosodimethylamine and 1,2-dimethylhydrazine were shown to injure lethally primary monolayer cultures of rat hepatocytes only after incubation periods in excess of 24 hr. The toxic action of these agents, therefore, mimics the time dependency of their hepatoxicity in vivo. The viability of hepatocytes treated with N-nitrosomethylbenzylamine was not different from controls at times up to 54 hr following treatment, a result which is also consistent with the inability of this compound to produce hepatotoxicity in vivo.
Asunto(s)
Carcinógenos/toxicidad , Dimetilhidrazinas/toxicidad , Dimetilnitrosamina/toxicidad , Hígado/efectos de los fármacos , Metilhidrazinas/toxicidad , 1,2-Dimetilhidrazina , Animales , Supervivencia Celular/efectos de los fármacos , Células Cultivadas/efectos de los fármacos , Células Cultivadas/enzimología , L-Lactato Deshidrogenasa/metabolismo , Hígado/enzimología , Masculino , Ratas , Ratas Endogámicas F344 , Ratas Endogámicas , Factores de TiempoRESUMEN
Methylation in vitro of calf thymus DNA, a supercoiled plasmid, poly(dG).poly(dC), and poly(dGdC).poly(dGdC) by N-nitroso(acetoxy-methyl)methylamine and N-nitroso(acetoxybenzyl)methylamine in the presence of esterase, and by N-nitrosomethylurea was investigated. Although there were differences in the amounts of 7-methylguanine and O6-methylguanine formed in the various DNA substrates, the methylation pattern was the same for each of these methylating agents. The three compounds reacted identically when methylation of a portion of a 345 bp restriction fragment of the plasmid pBR322 was examined at nucleotide resolution by a sequencing assay. They also showed a tendency to react preferentially with particular guanines. These data suggest that the three N-nitroso compounds methylate DNA via a common intermediate such as the methyl diazonium ion, which exhibits some sequence specificity.