[In vitro study of estradiol-linked nitrosourea in breast cancers in the mouse, rat and human: interspecies comparison].

In vitro activity of 1-(2-chloroethyl)-1-nitrosocarbamoyl-L-alanine-oestradiol-17-ester (CNC-ala-17-E2) at three concentrations in transplanted MXT mammary carcinoma in 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 percent of MXT tumours showed a more than 70% inhibition of colony formation in response to CNC-ala-17-E2. The MNU-induced model did not show this high degree of inhibition; only 5% of tumours showed an inhibition of up to 70%, but a superiority of the hormone-linked agent over the unlinked single agents was nevertheless discernible. By contrast, in human breast carcinomas there was no statistically superior response to the hormone-linked preparation as opposed to the single agents. Thus, in MXT mammary carcinoma the in vitro results parallelled previous findings in vivo, whereas in the MNU-induced autochthonous tumour 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.