Modulation of cytosolic sexual steroid receptors in autochthonous methylnitrosourea-induced rat mammary carcinoma following application of 2-chloroethylnitrosocarbamoyl-L-alanine linked to oestradiol or dihydrotestosterone.
This study concentrated on the influence of 2-chloroethylnitrosocarbamoyl-L-alanine (CNC-L-ala) linked to oestradiol (CNA-L-ala-E2) or dihydrotestosterone (CNC-L-ala-DHT) in position 17 of the respective steroid hormone on tumour growth and receptor kinetics of methylnitrosourea-induced rat mammary carcinoma. Both compounds almost completely arrested logarithmically growing mammary carcinoma of Sprague-Dawley rats: in the first week CNC-L-ala-E2 blocked the growth of these tumours by 92% compared to untreated control animals while, in animals treated with the physically equimolar mixture of CNC-L-ala and oestradiol (positive control), tumour growth was inhibited by 51% only. CNC-L-ala-DHT arrested the tumour growth in the first week by 95%, while the respective positive control (CNC-L-ala plus dihydrotestosterone) effected a growth inhibition of 71% compared to the untreated control. These results correlate well with the influence of both drugs on the cytosolic receptor content of sexual steroid hormones in the tumours. CNC-L-ala-E2 depleted the content of oestradiol receptors and kept it down for a week, while concomitantly the content of progesterone receptors increased considerably and that of androgen receptors showed a short-lived decrease. CNC-L-ala-DHT depleted androgen receptors as well as progesterone receptors. The content of androgen receptors remained low for a week, while that of progesterone receptors recovered within 8 days. The content of oestrogen receptors showed a moderate decrease.
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Institute of Toxicology and Chemotherapy, German Cancer Research Centre, Heidelberg, FRG.
Berger
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MR
Betsch
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Floride
J A
JA
Brix
H P
HP
Schmähl
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D
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D013196:Dihydrotestosterone / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D008770:Methylnitrosourea / Q000494:pharmacology; D009374:Neoplasms, Experimental / Q000139:chemically induced; D009588:Nitrogen Mustard Compounds / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011944:Receptors, Androgen / Q000187:drug effects*; D011959:Receptors, Estradiol / Q000187:drug effects*; D011987:Receptors, Steroid / Q000187:drug effects*
D000970:Antineoplastic Agents; D009588:Nitrogen Mustard Compounds; D011944:Receptors, Androgen; D011959:Receptors, Estradiol; D011987:Receptors, Steroid; D013196:Dihydrotestosterone; D004958:Estradiol; D008770:Methylnitrosourea; C065508:2-chloroethylnitrosocarbamoylalanine 17-dihydrotestosterone ester; C056364:1-(2-chloroethyl)-1-nitrosocarbamoylalanine estradiol-17-ester