Thermal melting of chromatin from the pancreas and liver of guinea pigs treated with 1-methyl-1-nitrosourea

Abstract

The carcinogen 1-methyl-1-nitrosourea (MNU) can cause pancreatic cancer in guinea pigs. We have examined the relative damage produced by MNU treatment on the chromatin from pancreas and liver of these animals. Thermal denaturation of chromatin from guinea pig pancreas and liver was studied following parenteral administration of MNU in several doses. Estimates of single strand breakage were also obtained by examination of the fluorescence of intercalated ethidium bromide. Oligomeric chromatin melted with a main T m at 78°C, with additional components at 48°C, 55°C and 65°C. Repetitive treatment with MNU at several doses between 20 mg/kg and 70 mg/kg produced destabilization of pancreatic chromatin as shown by a shift from 78°C to lower melting components. The liver by contrast was relatively unaffected. In addition, pancreatic chromatin showed an increase in alkali-induced strand unwinding with MNU treatment, probably due to an increase in single strand breaks, while there was no change in this regard in the liver. The data indicate that the pancreas is more susceptible to damage by MNU than the liver.