Tumor-Promoting Activity of 2,4-Dinitrofluorobenzene
Maldve, RE; Fischer, SM
| HERO ID | 2144422 |
|---|---|
| In Press | No |
| Year | 1995 |
| Title | Tumor-Promoting Activity of 2,4-Dinitrofluorobenzene |
| Authors | Maldve, RE; Fischer, SM |
| Journal | International Journal of Cancer |
| Volume | 60 |
| Issue | 4 |
| Page Numbers | 545-553 |
| Abstract | The tumor promoting activity of 2,4-dinitrofluorobenzene (70348) (DNFB) was studied in mice. DNFB at concentrations of 0, 0.05, 0.1, or 0.2% was applied to the shaved backs of female SENCAR-mice once or twice, the second dose given 3 days after the first. Other mice were similarly treated with 2 micrograms (microg) 12-O-tetradecanoylphorbol-13-acetate (TPA). The mice were killed 24 or 48 hours after the last dose and skinned. The treated skin areas were examined for histological changes and analyzed for ornithine-decarboxylase (ODC) activity. The RNA was extracted and analyzed for expression of mRNA for ODC, c-fos, and c-jun. Mice were topically administered 0 or 1microg TPA and administered 0 or 0.2% DNFB 3 days later. They were killed 15 to 48 hours later and the treated skin areas were removed and assayed for protein-kinase-C (PKC) and ODC activity. Partially purified PKC was incubated with 0 or 1microg per milliliters DNFB or TPA for up to 48 hr. The effects on PKC activity were determined. SENCAR-mice were initiated topically with 0 or 10 nanomoles 7,12-dimethylbenz(a)anthracene (DMBA) and then treated with 0, 0.1, or 0.2% DNFB or 0 or 1microg TPA twice weekly for 27 weeks. They were monitored for skin tumor development. DNFB given once at 0.1 or 0.2% induced mild epidermal hyperplasia. Two doses induced pronounced hyperplasia. DNFB caused a small increase in ODC activity relative to that of TPA. The second dose caused a large increase in ODC activity. DNFB and TPA significantly increased mRNA coding for ODC, c-fos, and c-jun. DNFB did not activate ODC in-vitro. In-vivo, DNFB alone significantly decreased PKC activity after 15 hours. By 48 hours, PKC activity had returned to the control value. In combination with TPA, ODC activity was increased by DNFB to a greater extent than by DNFB treatment alone. In DMBA initiated mice, 0.1 and 0.2% DNFB induced tumors in 65 and 85% of the mice, respectively. The tumor multiplicities were 2.0 and 3.2 tumors per mouse, respectively. TPA produced a 100% tumor incidence. The authors conclude that DNFB induces many of the same responses as TPA including cellular inflammation and proliferation and skin tumor promotion. The effects are independent of the PKC pathway. |
| Doi | 10.1002/ijc.2910600420 |
| Pmid | 7829270 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Scopus URL: https://www.scopus.com/inward/record.uri?eid=2-s2.0-0028909198&doi=10.1002%2fijc.2910600420&partnerID=40&md5=32b3a06e23410132c8efcc8986231b64 |
| Is Public | Yes |
| Language Text | English |