diethylstilbestrol
CAS RN 56-53-1
Cancer studies: Mammary gland tumors
Originating list
The list(s) or database(s) in which the chemical was identified as showing an
increase in mammary gland tumors. CPDB: Carcinogenic Potency Database, IARC:
International Agency for Research on Chemicals Monographs on the Evaluation of
Carcinogenic Risk of Chemicals to Man summaries, NTP TR: National Toxicology Program
(NTP) Technical Reports, NTP 11ROC: NTP 11th Report on Carcinogens, CCRIS: Chemical
Carcinogenesis Research Information Service.
Carcinogenicity Potency Database, IARC Monographs, National Toxicology Program 11th Report on Carcinogens, Chemical Carcinogenesis Research Information System
Mammary gland tumor summary
A summary of findings related to mammary gland tumors, most
often excerpted from IARC Monographs or the NTP 11th ROC, and, in some cases,
supplemented by our evaluation of individual studies and reviews, is available for the priority
chemicals and 67 others.
NTP 11ROC: "Several follow-up studies (including cohort studies and randomized clinical trials) found that women who took diethylstilbestrol at high doses during pregnancy were at increased risk for breast cancer. Some studies suggest that diethylstilbestrol-induced breast cancer may have a long latency period (15 to 20 years), but the evidence is inconclusive." "The evidence for increased risk of breast cancer in diethylstilbestrol daughters is inconclusive because of the young age of the cohort (Hatch et al. 1998, Palmer et al. 2002)." "Nevertheless, diethylstilbestrol continues to be used in clinical trials for treatment of prostate and breast cancer (Smith et al. 1998, Peethambaram et al. 1999)" "Prenatal exposure also caused mammary-gland tumors in mice." "When administered orally, diethylstilbestrol caused mammary-gland tumors in mice and rats. Subcutaneous injections or implants of diethylstilbestrol increased the incidences of mammary-gland tumors in mice and rats"
Only review sources are listed for this chemical because of lower likelihood of exposure.
Citation
Source Type
Notes
International Agency for Research on Cancer, Monographs on the evaluation of carcinogenic risk of chemicals to man.VOL.: Supplement 7 (1987) (p. 273) Oestrogens, Nonsteroidal. Summary of Data Reported and Evaluation.
Review
Mice treated prenatally with DES developed mammary tumors [ref: 23-28]. Prenatal exposure to DES potentiated mammary tumorigenesis in rats given 7,12-dimethylbenz[a]anthracene at about 50 days of age [ref: 36]. Rats given DES by subcutaneous pellet developed mammary tumors. When these animals were also treated with X-rays or neutrons, they developed a higher incidence of mammary tumours [ref: 37-39]. In other studies (subcutaneous, transplacental, oral), rats treated with DES developed mammary, hepatic and pituitary tumours [ref: 40-44].
23. McLachlan, J.A. (1979) Transplacental effects of diethylstilbestrol in mice. Natl Cancer Inst. Monogr., 51, 67-72
24. McLachlan, J.A., Newbold, R.R. & Bullock, B.C. (1980) Long-term effects on the female mouse genital tract associated with prenatal exposure to diethylstilbestrol. Cancer Res., 40, 3988-3999
25. Lamb, J.C., IV, Newbold, R.R. & McLachlan, J.A. (1981) Visualization by light and scanning electron microscopy of reproductive tract lesions in female mice treated transplacentally with diethylstilbestrol. Cancer Res., 41, 4057-4062
26. Newbold, R.R. & MacLachlan, J.A. (1982) Vaginal adenosis and adenocarcinoma in mice exposed prenatally or neonatally to diethylstilbestrol. Cancer Res., 42, 2003-2011
27. Walker, B.E. (1983) Uterine tumors in old female mice exposed prenatally to diethylstilbestrol. J. natl Cancer Inst., 70, 477-484
28. Nagasawa, H., Mori, T. & Nakajima, Y. (1980) Long-term effects of progesterone or diethylstilbestrol with or without estrogen after maturity on mammary tumorigenesis in mice. Eur. J. Cancer, 16, 1583-1589
36. Boylan, E.S. & Calhoon, R.E. (1979) Mammary tumorigenesis in the rat following prenatal exposure to diethylstilbestrol and postnatal treatment with 7,12-dimethylbenz(a)anthracene. J. Toxicol. environ. Health, 5, 1059-1071
37. Holtzman, S., Stone, J.P. & Shellabarger, C.J. (1979) Synergism of diethylstilbestrol and radiation in mammary carcinogenesis in female F344 rats. J. natl Cancer Inst., 63, 1071-1074
38. Holtzman, S., Stone, J.P. & Shellabarger, C.J. (1981) Synergism of estrogens and X-rays in mammary carcinogenesis in female ACI rats. J. natl Cancer Inst., 67, 455-459
39. Shellabarger, C.J., Chmelevsky, D., Kellerer, A.M., Stone, J.P. & Holtzman, S. (1982) Induction of mammary neoplasms in the ACI rat by 430-keV neutrons, X-rays, and diethylstilbestrol. J. natl Cancer Inst., 69, 1135-1146
40. Sumi, C., Yokoro, K. & Matsushima, R. (1983) Induction of hepatic tumors by diethylstilbestrol alone or in synergism with N-nitrosobutylurea in castrated male WF rats. J. natl Cancer Inst., 70, 937-942
41. Phelps, C. & Hymer, W.C. (1983) Characterization of estrogen-induced adenohypophyseal tumors in the Fischer 344 rat. Neuroendocrinology, 37, 23-31
42. Rothschild, T.C., Calhoon, R.E. & Boylan, E.S. (1985) Transplacental carcinogenicity of diethylstilbestrol (DES) in female ACI rats (Abstract No. 770). Proc. Am. Assoc. Cancer Res., 26, 195
43. Inoh, A., Kamiya, K., Fujii, Y. & Yokoro, K. (1985) Protective effects of progesterone and tamoxifen in estrogen-induced mammary carcinogenesis in ovariectomized W/FU rats. Jpn. J. Cancer Res. (Gann), 76, 699-704
44. Wanless, I.R. & Medline, A. (1982) Role of estrogens as promoters of hepatic neoplasia. Lab. Invest., 46, 313-320
National Toxicology Program 11th Report on Carcinogens. Diethylstilbestrol
Review
Prental exposure caused mammary gland tumors in mice. When administered orally, caused mammary-gland tumors in mice and rats. When administered by subcutaneous injection or implants, increased incidence of mammary gland tumors in mice and rats (IARC 1974, 1979, 1987).
National Toxicology Program 11th Report on Carcinogens, Table 1. Chemicals nominated to the National Toxicology Program for in-depth toxicological evaluation for carcinogenesis testing in fiscal years 1988-2003.
Review
Not nominated for NTP testing in 1998-2003.
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