Reference SummaryNewbold RR, Carcinogenesis 2000 Jul;21(7):1355-63
Title |
Proliferative lesions and reproductive tract tumors in male descendants of mice exposed developmentally to diethylstilbestrol. | ||||
Authors |
Newbold RR; Hanson RB; Jefferson WN; Bullock BC; Haseman J; McLachlan JA | ||||
Journal |
Carcinogenesis | ||||
Volume |
21 | ||||
Issue |
7 | ||||
Year |
2000 | ||||
Pages |
1355-63 | ||||
Abstract |
Prenatal exposure to diethylstilbestrol (DES) is associated with reproductive tract abnormalities, subfertility and neoplasia in experimental animals and humans. Studies using experimental animals suggest that the carcinogenic effects of DES may be transmitted to succeeding generations. To further evaluate this possibility and to determine if there is a sensitive window of exposure, outbred CD-1 mice were treated with DES during three developmental stages: group 1 was treated on days 9-16 of gestation (2.5, 5 or 10 microg/kg maternal body weight) during major organogenesis; group II was treated once on day 18 of gestation (1000 microg/kg maternal body weight) just prior to birth; and group III was treated on days 1-5 of neonatal life (0.002 microg/pup/day). DES-exposed female mice (F(1)) were raised to maturity and bred to control males to generate DES-lineage (F(2)) descendants. The F(2) males obtained from these matings are the subjects of this report; results in F(2) females have been reported previously [Newbold et al. (1998) CARCINOGENESIS:, 19, 1655-1663]. Reproductive performance of F(2) males when bred to control females was not different from control males. However, in DES F(2) males killed at 17-24 months, an increased incidence of proliferative lesions of the rete testis and tumors of the reproductive tract was observed. Since these increases were seen in all DES treatment groups, all exposure periods were considered susceptible to perturbation by DES. These data suggest that, while fertility of the DES F(2) mice appeared unaltered, increased susceptibility for tumors is transmitted from the DES 'grandmothers' to subsequent generations. | ||||
Links |
J:62956 – MGI References 10874014 – National Library of Medicine/PubMed |
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Strain Notes
|
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| Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
|---|---|---|---|---|---|
| CD-1 | Ampullary gland hyperplasia |
|
Ampullary gland |
1.6 |
|
| CD-1 | Blood vessel hemangioma |
|
Testis |
1.6 |
|
| CD-1 | Connective tissue - Fibroblast fibrosarcoma |
|
Mammary gland |
observed |
|
| CD-1 | Lung tumor | Lung |
12 |
||
| CD-1 | Lung tumor |
|
Lung |
21 - 38 |
|
| CD-1 | Mesodermal cell/mesoblast sarcoma |
|
Seminal vesicle |
3.4 |
|
| CD-1 | Prostate gland - Anterior lobe hyperplasia |
|
Prostate gland - Anterior lobe |
3.4 |
|
| CD-1 | Prostate gland hyperplasia | Prostate gland |
2.9 |
||
| CD-1 | Prostate gland hyperplasia |
|
Prostate gland |
3.4 - 9.0 |
|
| CD-1 | Prostate gland tumor |
|
Prostate gland |
3.4 |
|
| CD-1 | Seminal vesicle carcinosarcoma |
|
Seminal vesicle |
2.0 |
|
| CD-1 | Seminal vesicle hyperplasia |
|
Seminal vesicle |
2.0 - 3.4 |
|
| CD-1 | Seminal vesicle papilloma |
|
Seminal vesicle |
1.0 |
|
| CD-1 | Testis - Leydig cell (Interstitial cell) hyperplasia |
|
Testis - Leydig cell (Interstitial cell) |
1.5 - 6.9 |
|
| CD-1 | Testis - Leydig cell (Interstitial cell) tumor | Testis - Leydig cell (Interstitial cell) |
1.5 |
||
| CD-1 | Testis - Leydig cell (Interstitial cell) tumor |
|
Testis - Leydig cell (Interstitial cell) |
1.5 - 3.2 |
|
| CD-1 | Testis - Rete testis hyperplasia | Testis - Rete testis |
5.7 |
||
| CD-1 | Testis - Rete testis hyperplasia |
|
Testis - Rete testis |
7.7 - 35 |
|
| CD-1 | Testis - Rete testis hyperplasia - lipoid |
|
Testis - Rete testis |
1.9 |
|
| CD-1 | Testis - Rete testis tumor |
|
Testis - Rete testis |
1.2 - 1.9 |
|
| CD-1 | Testis - Seminiferous tubules hyperplasia |
|
Testis - Seminiferous tubules |
1.4 |