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Comparative Study
. 2011 Jun;4(6):890-6.
doi: 10.1158/1940-6207.CAPR-10-0369. Epub 2011 Mar 7.

Results from a dose-response study using 3,3'-diindolylmethane in the K14-HPV16 transgenic mouse model: cervical histology

Daniel W Sepkovic  1 , Johann Stein, Antoine D Carlisle, H Barbara Ksieski, Karen Auborn, Laura Raucci, Themba Nyirenda, H Leon Bradlow
Affiliations
Comparative Study

Results from a dose-response study using 3,3'-diindolylmethane in the K14-HPV16 transgenic mouse model: cervical histology

Daniel W Sepkovic et al. Cancer Prev Res (Phila). 2011 Jun.

Abstract

The human papilloma virus is the major cause of cervical cancer. Viral infection initiates cervical intraepithelial neoplasia, which progresses through several stages to cervical cancer. The objective of this study is to identify the minimum effective dose of diindolylmethane that prevents the progression from cervical dysplasia to carcinoma in situ. We document cervical histology in K14-HPV16 mice receiving different doses of diindolylmethane. Urinary diindolylmethane concentrations are reported. Diindolylmethane could enhance the efficacy of human papilloma virus vaccines, creating a new therapeutic use for these vaccines in women already infected with the virus. Five doses (0-2,500 ppm) of diindolylmethane were incorporated into each mouse diet. The reproductive tract was serially sectioned and urine was obtained for analysis of urinary diindolylmethane. The results indicate that 62% of mice receiving 1,000 ppm diindolylmethane remained dysplasia-free after 20 weeks compared with 16% of mice receiving no diindolylmethane and 18% receiving 500 ppm; 1,000 ppm of 3,3'-diindolylmethane in the diet completely suppressed the development of cervical cancer. Urinary diindolylmethane levels increased significantly as diindolylmethane in food increased. These findings imply usefulness for diindolylmethane in the search to prevent cervical cancer when used in combination with prophylactic or therapeutic vaccines.

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Figures

Figure 1
Figure 1. Histo-Pathological Analysis No DIM-0ppm 5X
Comparision of the cervical epithelium in wild type and transgenic mice receiving 0ppm DIM in the diet for 20 weeks. The wild type (left panel) shows a normal cervical epithelium. In the transgenic mouse (right panel) carcinoma in situ is illustrated.
Figure 2
Figure 2. Histo-Pathological Analysis DIM-1000ppm 5X
Comparision of the cervical epithelium in wild type and transgenic mice receiving 1000ppm DIM in the diet for 20 weeks. The wild type (left panel) shows a normal cervical epithelium. In the transgenic mouse (right panel) normal cervical epithelium is shown.
Figure 3
Figure 3. Concentrations of DIM in Transgenic and Wild type Mice From Each Dose Groupg
Box plots of DIM Levels at each DIM dose in transgenic and wild type mice. Jonckheere-Terpstra trend test result: both type reported significant trends (P<0.0001). Modified Mann-Whitney test was used to significant effect of each DIM dose cumulatively. Both transgenic and wild type reported significant dose effect (P<0.05) at consecutive DIM treated groups.
See this image and copyright information in PMC

References

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