In vivo influence of androgens on the cell kinetics and chromatin pattern of the MXT mouse mammary tumor treated or not by aminoglutethimide.
We characterized the influence of androstenedione, 5-alpha-dihydrotestosterone and 17-beta-estradiol on the chromatin organization and the cell kinetics (distribution of the cells into the G0-G1, S and G2+ M fractions) of MXT mouse mammary tumors grafted onto animals that were left intact or that were oophorectomized and/or treated with aminoglutethimide. The cell kinetics and chromatin pattern were monitored by analyzing Feulgen-stained MXT imprint smears through a cell image processor, the SAMBA 200 system. We have also assayed the estrogen and progesterone receptors of these MXT tumors, which appeared to possess both of these biological markers. Our results show that ovariectomy or aminoglutethimide treatment slowed down the MXT tumor growth without any additive effect between them. Androstenedione exerted a stimulating influence on the cell kinetics, which were very similar to those observed after estradiol administration; the treatment of castrated animals with aminoglutethimide completely abolished this androstenedione-induced stimulating influence, however. This androgen lacked any apparent efficiency to transform cell nuclei from a state of castration-induced chromatin condensation into a thinly textured and decondensed state, as did estradiol. Dihydrotestosterone was able to activate the cell kinetics of MXT tumor grafted onto castrated animals as well as those of MXT neoplasms grafted on oophorectomized mice treated with aminoglutethimide. Dihydrotestosterone also possesses the property to transform condensed chromatin into decondensed chromatin. It thus appeared that androstenedione and dihydrotestosterone could activate MXT cell proliferation, as did estradiol, although it appeared that their mechanisms of action were quite distinct from each other.
de Launoit
Y
Y
Laboratoire d'Histologie, Faculté de Médecine, Université Libre de Bruxelles, Belgium.
Kiss
R
R
D000616:Aminoglutethimide / Q000494:pharmacology*; D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D047072:Aromatase Inhibitors; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002843:Chromatin / Q000032:analysis*; D004396:Coloring Agents; D008325:Mammary Neoplasms, Experimental / Q000473:pathology* / Q000648:ultrastructure; D051379:Mice; D008815:Mice, Inbred Strains; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012394:Rosaniline Dyes; D013194:Staining and Labeling; D013223:Statistics as Topic; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000728:Androgens; D047072:Aromatase Inhibitors; D002843:Chromatin; D004396:Coloring Agents; C007722:Feulgen stain; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D012394:Rosaniline Dyes; D000616:Aminoglutethimide