Interaction of bis- and mono-N-nitrosoureas with rat liver chromatin in vitro.

The effects of nine N-nitrosoureas (three bis-N-nitrosoureas, five mono-N-nitrosoureas and chloroethyl-N-nitrosourea) on the template activity of rat liver chromatin and Escherichia coli DNA were compared. The template activity of rat liver chromatin was inhibited by some N-nitrosoureas that have relatively strong alkylating activity. The inhibitory effects with respect to E. coli DNA were stronger than those with respect to rat liver chromatin. The inhibitory effects had a tendency to decrease with increasing length of the alkyl chain. The template activity of rat liver chromatin was slightly increased by some N-nitrosoureas, potassium cyanate and some alkyl isocyanates. The chromatin reacting with 1,1'-ethylene-bis-(1-nitrosourea) was more sensitive than the control chromatin to DNase 1 and Staphylococcal nuclease. The solubility of chromatin carbamoylated by 1,1'-ethylene-bis-(1-nitrosourea) was clearly higher than that of control chromatin in the presence of magnesium or calcium ion.