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Inhibition of 7-Bromomethylbenzaanthracene-promoted Mouse Skin Tumor Formation by Retinoic Acid and Dexamethasone

Inhibition of 7-Bromomethylbenzaanthracene-promoted Mouse Skin Tumor Formation by Retinoic Acid... Retinoic acid, a potent inhibitor of mouse skin tumor promotion by 12- O -tetradecanoylphorbol-13-acetate, fails to inhibit tumor formation by the complete carcinogen, 7,12-dimethylbenzaanthracene (DMBA). To obtain further clues about the nature of the mechanism of the carcinogenic process as well as the mechanism of the effect of retinoic acid on tumor promotion, the effect of retinoic acid and two other modifiers (dexamethasone and 7,8-benzoflavone) of tumor formation on tumor promotion by 7-bromomethylbenzaanthracene (BrMBA) was determined. BrMBA, a structural analogue of DMBA, is a weak mouse skin tumor-initiating agent but is a good skin tumor promoter. Application of 10, 100, and 200 nmol of BrMBA twice weekly to DMBA-initiated skin resulted in 0, 1.6, and 2.5 papillomas per mouse, and 0, 44, and 60% of mice had papillomas at the 25th week of promotion treatment, respectively. Application of 17 nmol of retinoic acid or 76 nmol of dexamethasone 30 min prior to each twice weekly application of 100 nmol of BrMBA to DMBA-initiated skin inhibited the formation of skin papillomas by 73 and 100%, respectively. 7,8-Benzoflavone, at a 367-nmol dose, did not inhibit tumor promotion by BrMBA. Application of 200 nmol of BrMBA to mouse skin induced epidermal omithine decarboxylase activity; a peak activity was observed between 8 and 18 hr following BrMBA treatment. Application of 17 nmol of retinoic acid or 76 nmol of dexamethasone inhibited the induction of ornithine decarboxylase activity by BrMBA. 7,8-Benzoflavone did not inhibit the induction of ornithine decarboxylase activity by BrMBA. Retinoic acid and dexamethasone, which inhibit tumor promotion by 12- O -tetradecanoylphorbol-13-acetate, also inhibited tumor promotion by BrMBA, but the nature of the mechanism of tumor promotion by BrMBA is unclear; BrMBA did not inhibit specific binding of 12- O - 3 Htetradecanoylphorbol-13-acetate to the cellular membrane fraction of mouse epidermis. 1 The work was supported by Grants CA-07175 and CA-22484 from the NIH. 2 Present address: Department of Human Oncology, Wisconsin Clinical Cancer Center, University of Wisconsin Center for Health Sciences K4/538, 600 Highland Avenue, Madison, Wis. 53792. To whom requests for reprints should be addressed. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Cancer Research American Association of Cancer Research

Inhibition of 7-Bromomethylbenzaanthracene-promoted Mouse Skin Tumor Formation by Retinoic Acid and Dexamethasone

Inhibition of 7-Bromomethylbenzaanthracene-promoted Mouse Skin Tumor Formation by Retinoic Acid and Dexamethasone

Cancer Research , Volume 43 (7): 3045 – Jul 1, 1983

Abstract

Retinoic acid, a potent inhibitor of mouse skin tumor promotion by 12- O -tetradecanoylphorbol-13-acetate, fails to inhibit tumor formation by the complete carcinogen, 7,12-dimethylbenzaanthracene (DMBA). To obtain further clues about the nature of the mechanism of the carcinogenic process as well as the mechanism of the effect of retinoic acid on tumor promotion, the effect of retinoic acid and two other modifiers (dexamethasone and 7,8-benzoflavone) of tumor formation on tumor promotion by 7-bromomethylbenzaanthracene (BrMBA) was determined. BrMBA, a structural analogue of DMBA, is a weak mouse skin tumor-initiating agent but is a good skin tumor promoter. Application of 10, 100, and 200 nmol of BrMBA twice weekly to DMBA-initiated skin resulted in 0, 1.6, and 2.5 papillomas per mouse, and 0, 44, and 60% of mice had papillomas at the 25th week of promotion treatment, respectively. Application of 17 nmol of retinoic acid or 76 nmol of dexamethasone 30 min prior to each twice weekly application of 100 nmol of BrMBA to DMBA-initiated skin inhibited the formation of skin papillomas by 73 and 100%, respectively. 7,8-Benzoflavone, at a 367-nmol dose, did not inhibit tumor promotion by BrMBA. Application of 200 nmol of BrMBA to mouse skin induced epidermal omithine decarboxylase activity; a peak activity was observed between 8 and 18 hr following BrMBA treatment. Application of 17 nmol of retinoic acid or 76 nmol of dexamethasone inhibited the induction of ornithine decarboxylase activity by BrMBA. 7,8-Benzoflavone did not inhibit the induction of ornithine decarboxylase activity by BrMBA. Retinoic acid and dexamethasone, which inhibit tumor promotion by 12- O -tetradecanoylphorbol-13-acetate, also inhibited tumor promotion by BrMBA, but the nature of the mechanism of tumor promotion by BrMBA is unclear; BrMBA did not inhibit specific binding of 12- O - 3 Htetradecanoylphorbol-13-acetate to the cellular membrane fraction of mouse epidermis. 1 The work was supported by Grants CA-07175 and CA-22484 from the NIH. 2 Present address: Department of Human Oncology, Wisconsin Clinical Cancer Center, University of Wisconsin Center for Health Sciences K4/538, 600 Highland Avenue, Madison, Wis. 53792. To whom requests for reprints should be addressed.

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Publisher
American Association of Cancer Research
Copyright
Copyright © 1983 by the American Association for Cancer Research.
ISSN
0008-5472
Publisher site

Abstract

Retinoic acid, a potent inhibitor of mouse skin tumor promotion by 12- O -tetradecanoylphorbol-13-acetate, fails to inhibit tumor formation by the complete carcinogen, 7,12-dimethylbenzaanthracene (DMBA). To obtain further clues about the nature of the mechanism of the carcinogenic process as well as the mechanism of the effect of retinoic acid on tumor promotion, the effect of retinoic acid and two other modifiers (dexamethasone and 7,8-benzoflavone) of tumor formation on tumor promotion by 7-bromomethylbenzaanthracene (BrMBA) was determined. BrMBA, a structural analogue of DMBA, is a weak mouse skin tumor-initiating agent but is a good skin tumor promoter. Application of 10, 100, and 200 nmol of BrMBA twice weekly to DMBA-initiated skin resulted in 0, 1.6, and 2.5 papillomas per mouse, and 0, 44, and 60% of mice had papillomas at the 25th week of promotion treatment, respectively. Application of 17 nmol of retinoic acid or 76 nmol of dexamethasone 30 min prior to each twice weekly application of 100 nmol of BrMBA to DMBA-initiated skin inhibited the formation of skin papillomas by 73 and 100%, respectively. 7,8-Benzoflavone, at a 367-nmol dose, did not inhibit tumor promotion by BrMBA. Application of 200 nmol of BrMBA to mouse skin induced epidermal omithine decarboxylase activity; a peak activity was observed between 8 and 18 hr following BrMBA treatment. Application of 17 nmol of retinoic acid or 76 nmol of dexamethasone inhibited the induction of ornithine decarboxylase activity by BrMBA. 7,8-Benzoflavone did not inhibit the induction of ornithine decarboxylase activity by BrMBA. Retinoic acid and dexamethasone, which inhibit tumor promotion by 12- O -tetradecanoylphorbol-13-acetate, also inhibited tumor promotion by BrMBA, but the nature of the mechanism of tumor promotion by BrMBA is unclear; BrMBA did not inhibit specific binding of 12- O - 3 Htetradecanoylphorbol-13-acetate to the cellular membrane fraction of mouse epidermis. 1 The work was supported by Grants CA-07175 and CA-22484 from the NIH. 2 Present address: Department of Human Oncology, Wisconsin Clinical Cancer Center, University of Wisconsin Center for Health Sciences K4/538, 600 Highland Avenue, Madison, Wis. 53792. To whom requests for reprints should be addressed.

Journal

Cancer ResearchAmerican Association of Cancer Research

Published: Jul 1, 1983

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