In vitro evaluation of an estradiol-linked nitrosourea in mammary carcinomas of mouse, rat and man.

In vitro activity of 1-(2-chloroethyl)-1-nitrosocarbamoyl-L-alanine-estradiol-17-ester (CNC-ala-17-E2) at three concentrations in transplanted MXT mammary carcinoma in B6D2F1 mice and autochthonous methylnitrosourea (MNU)-induced mammary carcinoma in Sprague-Dawley rats, as well as in 30 human primary breast carcinomas using the bilayer soft agar assay is described. Eighty-five per cent of MXT tumors showed a more than 70% inhibition of colony formation following CNC-ala-17-E2. In the MNU-induced model this high degree of inhibition was not observed: only 5% of individual tumors showed an inhibition up to 70%, but a superiority of the hormone-linked agent over the unlinked single agents was nevertheless discernible. In contrast, in human breast carcinomas a response at this sensitivity level could not be assessed. Thus, in the MXT mammary carcinoma the in vitro results paralleled previous findings in vivo, whereas in the MNU-induced autochthonous tumor model this close in vivo-in vitro correlation was not observed. The discrepancy between in vivo and in vitro results found in the autochthonous rat model indicates that hormone-linked nitrosoureas should not necessarily be abandoned for the treatment of human breast carcinoma on the basis of negative in vitro results alone.