Comparative C19-radiosteroid metabolism by MA 160 and HeLa cell lines |
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Authors: | P Ofner R L Vena N J Barowsky R M Singer A H Tashjian Jr |
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Institution: | (1) Steroid Biochemistry Laboratory, Lemuel Shattuck Hospital, Boston, Massachusetts 02130;(2) Department of Urology, Tufts University School of Medicine, 02111 Boston, Massachusetts;(3) Laboratory of Pharmacology, Harvard School of Dental Medicine, and Department of Pharmacology, Harvard Medical School, 02115 Boston, Massachusetts;(4) Steroid Biochemistry Laboratory, Lemuel Shattuck Hospital, 170 Morton Street, 02130 Jamaica Plain, Massachusetts;(5) Tufts Cancer Research Center, and Department of Pathology, Tufts University School of Medicine, 02111 Boston, Massachusetts;(6) Present address: School of Dentistry, Department of Anatomy, Fairleigh Dickinson University, 07601 Hackensack, New Jersey |
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Abstract: | Summary Since the designation of the human MA 160 line as prostatic epithelial cells has been questioned and the possibility of HeLa
cross contamination raised, this comparative study of C19-radiosteroid transformation in MA 160 and HeLa monolayer cultures was done to determine whether these cells possess the distinguishing
features of reductive and oxidative androgen metabolism expected in male and female genital organs, respectively. We compared
the radiometabolite patterns produced by incubating 14C]testosterone (300nM) and 3H]testosterone (3nm) and 5α-dihydrotestosterone (17β-hydroxy-5α-androstan-3-one) with cultures of prostatic MA 160 and HeLa Parent, TCRC-1, TCRC-2
and ATC 229 cells. C19-Radiosteroid metabolite patterns from MA 160 cell incubations also were compared with patterns generated by MA 196 fibroblasts
from abdomnal skin of the same donor. MA 160 cells metabolized radiotestosterone predominantly to 5α-dihydrotestosterone,
5α-androstane-3α,17β-diol and 5α-androstane-3β,17β-diol. The diol epimers were the principal metabolites of 5α-dihydrotestosterone
radiosubstrate. In contrast, radiotestosterone metabolism by MA 196 and HeLa Parent, TCRC-1 and TCRC-2 cells was overwhelmingly
to the 17-oxosteroids 4-androstene-3,17-dione and androsterone. Another pathway was operative in HeLa 229 and, to a minor
extent, in TCRC-1, which converted radiotestosterone to 4-androstene-3α,17β-diol and 5α-androstane-3α,17β-dol, with little
formation of 5α-dihydrotestosterone. MA 160 cells thus metabolize radiotestosterone preponderantly to 5α-reduced 17β-hydroxysteroids
as expected for prostatic epithelial cells, whereas HeLa cells show heterogeneity in metabolizing the labeled hormone by the
alternative 17-oxosteroid and Δ4 pathways.
This work was supported by Public Health Service Research Grants CA 13417 and CA 12924 from the National Cancer Institute,
AM 11011 from the National Institute of Arthritis, Metabolism and Digestive Diseases, and by appropriations of the Commonwealth
of Massachusetts, Item No. 4532-9003-01. |
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Keywords: | MA 160 cells HeLa cell lines monolayer culture radiotestosterone metabolism cross contamination |
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