Mechanistic Approaches to New Nitrosourea Development

Abstract

The 1-chloroethyl-1-nitrosoureas are highly active against nearly all experimental tumors that have been extensively tested in mice, rats, and hamsters [39]. The benefits against the human disease, however, have been relatively modest [4]. Although the activity in man has so far been disappointing, the high activity in animals suggests that there is greater potential to be tapped. The nitrosoureas are known to react with DNA, as well as with other cellular macromolecules [5, 31,33, 34,41,43,44]. If DNA is the critical target, some key mechanistic questions may yield to presently available experimental techniques. Some current concepts and results along this line of approach will be reviewed.