Biochemical and pharmacologic properties of nitrosoureas.

The employment of traditional biochemical and pharmacological concepts, together with the development of original molecular approaches, has created a more comprehensive understanding of the mechanism of action of nitrosoureas. For example, it is clear that all nuclear macromolecules are susceptible to alkylation and/or carbamoylation by nitrosoureas. The relative importance of these respective processes is equivocal, but there is evidence to suggest that the alkylating potential of these drugs is directly responsible for their cytotoxic, mutagenic, or carcinogenic properties. The structural organization of nuclear chromatin, either at the nucleosomal or function level, is a critical determinant when considering specific macromolecules as potential targets for nitrosourea interaction. Perhaps a more complete understanding of the nuclear architecture of specific cell types will lead to a more precise understanding of nitrosourea selectivity, especially with respect to the nonmyelotoxic properties of chlorozotocin. Such knowledge would also assist in the rational development of novel nitrosourea analogues.