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Primary cultures of prostate cells and their ability to activate carcinogens

Prostate Cancer and Prostatic Diseases volume 5, pages 96–104 (2002)Cite this article

Abstract

Differences in the incidence of prostate cancer (CaP) amongst different migrant populations point to causative agents of dietary and/or environmental origin. Prostate tissues were obtained following transurethral resection of the prostate (TURP) or radical retropubic prostatectomy. After surgery, TURP-derived or tumour-adjacent tissue fragments were minced in warm PFMR-4A medium (37°C) and suspensions pipetted into collagen-coated petri dishes. Non-adherent material was removed by washing with fresh medium after 12 h. Adhered cells subsequently reacted positively with monoclonal antibodies to prostate specific antigen (PSA). PSA was also detected in the medium. The genotoxicities of the chemical carcinogens 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP), its N-hydroxy metabolite (N-OH-PhIP) and benzo[a]pyrene (B[a]P) in adherent cell populations from different donors (n=8) were examined. Cells were treated in suspension for 30 min at 37°C in the presence of the DNA repair inhibitors hydroxyurea (HU) and cytosine arabinoside (ara-C). DNA single-strand breaks were detected in cells by the alkaline single cell-gel electrophoresis (‘Comet’) assay and quantified by measuring comet tail length (CTL) in μm. All three carcinogens induced dose-related increases in CTLs (P<0.0001) in cells from four donors 24 h post-seeding. However, in cells from a further two donors the genotoxic effects of PhIP, N-OH-PhIP and B[a]P were much less apparent after 48 h than after 24 h in culture. After 96 h in culture, cells from these donors appeared to be resistant to the comet-forming activity of the compounds. However, B[a]P-DNA adducts were still measurable by 32P-postlabelling for up to 14 days following a 24-h exposure to 50 μM B[a]P in adhered cells from another two donors. This study shows that primary cultures of cells derived from the prostate can activate members of two classes of chemical carcinogens. Further development may provide a robust model system in which to investigate the aetiology of CaP.

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Acknowledgements

This work was supported by the Association for International Cancer Research, the Cancer Research Campaign and the Department of Health. Francis L. Martin is currently supported by a grant from the North West Cancer Research Fund.

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Authors and Affiliations

  1. Institute of Cancer Research, Haddow Laboratories, Cotswold Road, Sutton, Surrey, UK

    F L Martin, K J Cole, P L Grover & D H Phillips

  2. Department of Urology, King's College Hospital, Denmark Hill, London, UK

    G H Muir & G G Kooiman

  3. Department of Drug Disposition, Lilly Corporate Center, Indianapolis, USA

    J A Williams

  4. Department of Clinical Biochemistry, King's College Hospital, Denmark Hill, London, UK

    R A Sherwood

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  1. F L Martin
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Correspondence to F L Martin.

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Martin, F., Cole, K., Muir, G. et al. Primary cultures of prostate cells and their ability to activate carcinogens. Prostate Cancer Prostatic Dis 5, 96–104 (2002). https://doi.org/10.1038/sj.pcan.4500579

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