Potentially carcinogenic analogues of the carcinogen hexamethylphosphoramide: evaluation in vitro.

Experiments conducted in vitro are described which indicate that a family of specifically substituted phosphoramides may share the carcinogenic properties displayed by the structurally novel carcinogen, hexamethylphosphoramide (HMPA). Most of the analogues tested only gave a positive response in vitro when using a substantially modified liver homogenate activation system (S-9 mix). The analogy drawn in our earlier paper between this new class of potential carcinogens and the nitrosamine carcinogens, has been strengthened. The following compounds gave a positive response in the cell transformation assay of Styles: hexamethylphosphoramide (HMPA), hexamethylphosphorous triamide, hexamethylphosphorothioic triamide, tripiperidinophosphine oxide, phosphorothioic trimorpholide and diethoxymorpholinophosphine oxide (DEMPA).