[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.
Petru
E
E
Institut für Toxikologie und Chemotherapie, Krebsforschungszentrum Heidelberg.
Berger
M R
MR
Zeller
W J
WJ
Kaufmann
M
M
D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy*; D002277:Carcinoma / Q000188:drug therapy*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000188:drug therapy*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003114:Colony-Forming Units Assay; D004958:Estradiol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D008770:Methylnitrosourea; D051379:Mice; D009368:Neoplasm Transplantation; D009588:Nitrogen Mustard Compounds / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D014407:Tumor Cells, Cultured / Q000187:drug effects*; D014410:Tumor Stem Cell Assay
D009588:Nitrogen Mustard Compounds; D004958:Estradiol; D008770:Methylnitrosourea; C056364:1-(2-chloroethyl)-1-nitrosocarbamoylalanine estradiol-17-ester
In-vitro-Untersuchung eines östradiolgekoppelten Nitrosoharnstoffes an Mammakarzinomen von Maus, Ratte und Mensch: Interspeziesvergleich.