Influence of chemopreventive agents on estradiol metabolism and mammary preneoplasia in the C3H mouse Journal Article
| Authors: | Osborne, M. P.; Telang, N. T.; Kaur, S.; Bradlow, H. L. |
| Article Title: | Influence of chemopreventive agents on estradiol metabolism and mammary preneoplasia in the C3H mouse |
| Abstract: | The C3H strain of mouse has a high incidence of murine mammary tumor virus-induced mammary tumors, and tumorigenesis progresses via the intermediate formation of the preneoplastic, hyperplastic alveolar nodules (HANs). The C3H mouse also exhibits an elevation in 16α-hydroxylation of estradiol which remains unaltered in relation to the age or presence of tumor, but which is detectable well before the emergence of overt mammary cancer. This metabolic pathway leads to the formation of 16α-hydroxyestrone (16α-OHE1), a putative promoter of mammary cancer. The present study examines the effect of two prototype chemopreventive agents, tamoxifen (TAM) and N-(4-hydroxyphenyl)retinamide (HPR), on 16α-hydroxylation of estradiol and on the growth of HANs. Treatment with TAM, HPR, or a combination of TAM and HPR for 4 weeks in 6- to 8-week-old C3H mice resulted in a consistent elevation in the 16α-hydroxylotion pathway of estradiol metabolism relative to the placebo control group (20.50% ± 2.35%, 21.46% ± 1.49%, 18.00% ± 7.75%, and 12.64% ± 1].45% SD, respectively) and in a significant decrease in the mean frequency of HANs per mammary gland (1.4, 2.1, 0.0, and 5.8, respectively). Mice without any experimental manipulation exhibited an age-dependent progressive increase in HAN frequency from 1.5 per gland at 4 weeks of age to 12.1 per gland at 24 weeks of age. Administration of TAM, HPR, or a combination of TAM and HPR up to 22 weeks of age resulted in a continued suppression of HAN frequency, and the two agents in combination exerted an additive effect on the suppression of HAN development. These results indicate that the promoting effect of 16α-OHE1 on mammary preneoplasia can be overridden by TAM and HPR, possibly due to the greater affinity of TAM relative to 16α-OHE1 for the cellular estrogen receptor, or to HPR-induced reduction in 16α-OHE1 susceptible target tissue (i.e., suppression of HANs). © 1990. |
| Keywords: | unclassified drug; nonhuman; animal cell; mouse; animal; mice; breast cancer; animalia; drug therapy, combination; hyperplasia; tamoxifen; aging; estradiol; mammary neoplasms, experimental; precancerous conditions; mice, inbred c3h; fenretinide; hydroxylation; steroids; tretinoin; subcutaneous drug administration; chemopreventive agents; female; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; estradiol metabolism; mammary prenoplasia; n (4 hydroxyphenyl)retinamide derivative |
| Journal Title: | Steroids |
| Volume: | 55 |
| Issue: | 3 |
| ISSN: | 0039-128X |
| Publisher: | Elsevier Inc. |
| Date Published: | 1990-03-01 |
| Start Page: | 114 |
| End Page: | 119 |
| Language: | English |
| DOI: | 10.1016/0039-128x(90)90006-w |
| PUBMED: | 2139751 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 27 January 2020 -- Source: Scopus |
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