CHARACTERIZATION OF THE TUMOR-PROMOTING ACTIVITY OF THAPSIGARGIN IN CF-1 MOUSE SKIN

  • Authors:
    • XM GAO
    • EM PERCHELLET
    • GL CHEN
    • SW NEWELL
    • JP PERCHELLET
  • View Affiliations

  • Published online on: October 1, 1994     https://doi.org/10.3892/ijo.5.4.793
  • Pages: 793-803
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Abstract

The ornithine decarboxylase (ODC), hydroperoxide (HPx) and DNA responses to 12-O-tetradecanoylphorbol-13-acetate (TPA) and mezerein (MEZ) are similar in vivo. Thapsigargin (TG) respectively mimics about 15, 75 and 75% of the ODC, HPx and DNA responses to TPA and these differences persist after chronic treatments. The peak of ODC induction 5 h after 2 TG treatments at 12 to 48-h intervals is twice that produced 16 h after a single TG treatment or 5 h after 2 TG treatments at a 72-h interval. The ODC-inducing activity of TG is dose dependent from 1 to 15 nmol and its magnitude is maximal after 2 applications. The biochemical effects of TG and TPA are neither synergistic nor additive. But the ODC response to TG is greater when this compound is applied 48 h after TPA than after another TG treatment. In initiated skins promoted 2x/week with 5 nmol of TPA, MEZ, or TG, the Ist papillomas (PAs) appear at 7, 12 and 17 weeks, the tumor incidences are 100, 40 and 24%, and there are 17, 1 and 0.6 PAs/mouse, respectively. The tumor-promoting activity of TG is increased at a higher dose (15 nmol), slightly accelerated at a higher frequency (1x/2 days) and decreased at a lower frequency (1x/week). TPA applied 1x/3 weeks is insufficient to promote tumors but slightly enhances the tumor-promoting activity of TG. MEZ applied 1x/4 weeks in stage 2 also accelerates the tumor-promoting activity of TG. TG is effective as a stage 1 promoter but its promoting activity is not enhanced by stage 1 treatments with TPA. In contrast to TPA or even MEZ, TG may be a very weak tumor promoter because it is a very weak ODC inducer and mobilizes enough intracellular free Ca2+ to impair tumor cell proliferation.

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October 1994
Volume 5 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
GAO, X., PERCHELLET, E., CHEN, G., NEWELL, S., & PERCHELLET, J. (1994). CHARACTERIZATION OF THE TUMOR-PROMOTING ACTIVITY OF THAPSIGARGIN IN CF-1 MOUSE SKIN. International Journal of Oncology, 5, 793-803. https://doi.org/10.3892/ijo.5.4.793
MLA
GAO, X., PERCHELLET, E., CHEN, G., NEWELL, S., PERCHELLET, J."CHARACTERIZATION OF THE TUMOR-PROMOTING ACTIVITY OF THAPSIGARGIN IN CF-1 MOUSE SKIN". International Journal of Oncology 5.4 (1994): 793-803.
Chicago
GAO, X., PERCHELLET, E., CHEN, G., NEWELL, S., PERCHELLET, J."CHARACTERIZATION OF THE TUMOR-PROMOTING ACTIVITY OF THAPSIGARGIN IN CF-1 MOUSE SKIN". International Journal of Oncology 5, no. 4 (1994): 793-803. https://doi.org/10.3892/ijo.5.4.793