Alterations in thermal stability of rat liver chromatin and DNA induced in vivo by dimethylnitrosamine and diethylnitrosamine.

A study was made of the effects of administration to rats of dimethylnitrosamine and diethylnitrosamine on the transition temperature (Tm) of sheared chromatin and DNA isolated from the liver. The analysis was made by thermal chromatography on hydroxylapatite with the use of DNA prelabeled with [3H]thymidine and following the elution pattern during the operation of a continuous temperature gradient. With a nonnecrogenic dose of dimethylnitrosamine (10 mg/kg), the alterations in chromatin were maximal at 24 hr and disappeared by 3 days. Greatest differences in elution profiles of chromatin after dimethylnitrosamine treatment were observed in the region above 80 degrees. Administration of the carcinogen caused a lowering of the "melting" curve in this region, the displacement from control position being proportional to the dose. The maximum dose (60 mg/kg) displaced the complete chromatin melting curve up to 5 degrees to the lower side. DNA isolated from this chromatin melted 3 degrees less than that from control rats. However, administration of lower doses of dimethylnitrosamine did not affect the melting profile of DNA. The administration of diethylnitrosamine caused a similar type of change. However, the modification was also seen at 50-60 degrees.