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Fetal Radiation Exposure Induces Testicular Cancer in Genetically Susceptible Mice

The prevalence of testicular germ cell tumors (TGCT), a common solid tissue malignancy in young men, has been annually increasing at an alarming rate of 3%. Since the majority of testicular cancers are derived from germ cells at the stage of transformation of primordial germ cell (PGC) into gonocyte...

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Autores principales: Shetty, Gunapala, Comish, Paul B., Weng, Connie C. Y., Matin, Angabin, Meistrich, Marvin L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278464/
https://www.ncbi.nlm.nih.gov/pubmed/22348147
http://dx.doi.org/10.1371/journal.pone.0032064
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author Shetty, Gunapala
Comish, Paul B.
Weng, Connie C. Y.
Matin, Angabin
Meistrich, Marvin L.
author_facet Shetty, Gunapala
Comish, Paul B.
Weng, Connie C. Y.
Matin, Angabin
Meistrich, Marvin L.
author_sort Shetty, Gunapala
collection PubMed
description The prevalence of testicular germ cell tumors (TGCT), a common solid tissue malignancy in young men, has been annually increasing at an alarming rate of 3%. Since the majority of testicular cancers are derived from germ cells at the stage of transformation of primordial germ cell (PGC) into gonocytes, the increase has been attributed to maternal/fetal exposures to environmental factors. We examined the effects of an estrogen (diethylstilbestrol, DES), an antiandrogen (flutamide), or radiation on the incidence of testicular germ cell tumors in genetically predisposed 129.MOLF-L1 (L1) congenic mice by exposing them to these agents on days 10.5 and 11.5 of pregnancy. Neither flutamide nor DES produced noticeable increases in testis cancer incidence at 4 weeks of age. In contrast, two doses of 0.8-Gy radiation increased the incidence of TGCT from 45% to 100% in the offspring. The percentage of mice with bilateral tumors, weights of testes with TGCT, and the percentage of tumors that were clearly teratomas were higher in the irradiated mice than in controls, indicating that irradiation induced more aggressive tumors and/or more foci of initiation sites in each testis. This radiation dose did not disrupt spermatogenesis, which was qualitatively normal in tumor-free testes although they were reduced in size. This is the first proof of induction of testicular cancer by an environmental agent and suggests that the male fetus of women exposed to radiation at about 5–6 weeks of pregnancy might have an increased risk of developing testicular cancer. Furthermore, it provides a novel tool for studying the molecular and cellular events of testicular cancer pathogenesis.
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spelling pubmed-32784642012-02-17 Fetal Radiation Exposure Induces Testicular Cancer in Genetically Susceptible Mice Shetty, Gunapala Comish, Paul B. Weng, Connie C. Y. Matin, Angabin Meistrich, Marvin L. PLoS One Research Article The prevalence of testicular germ cell tumors (TGCT), a common solid tissue malignancy in young men, has been annually increasing at an alarming rate of 3%. Since the majority of testicular cancers are derived from germ cells at the stage of transformation of primordial germ cell (PGC) into gonocytes, the increase has been attributed to maternal/fetal exposures to environmental factors. We examined the effects of an estrogen (diethylstilbestrol, DES), an antiandrogen (flutamide), or radiation on the incidence of testicular germ cell tumors in genetically predisposed 129.MOLF-L1 (L1) congenic mice by exposing them to these agents on days 10.5 and 11.5 of pregnancy. Neither flutamide nor DES produced noticeable increases in testis cancer incidence at 4 weeks of age. In contrast, two doses of 0.8-Gy radiation increased the incidence of TGCT from 45% to 100% in the offspring. The percentage of mice with bilateral tumors, weights of testes with TGCT, and the percentage of tumors that were clearly teratomas were higher in the irradiated mice than in controls, indicating that irradiation induced more aggressive tumors and/or more foci of initiation sites in each testis. This radiation dose did not disrupt spermatogenesis, which was qualitatively normal in tumor-free testes although they were reduced in size. This is the first proof of induction of testicular cancer by an environmental agent and suggests that the male fetus of women exposed to radiation at about 5–6 weeks of pregnancy might have an increased risk of developing testicular cancer. Furthermore, it provides a novel tool for studying the molecular and cellular events of testicular cancer pathogenesis. Public Library of Science 2012-02-13 /pmc/articles/PMC3278464/ /pubmed/22348147 http://dx.doi.org/10.1371/journal.pone.0032064 Text en Shetty et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Shetty, Gunapala
Comish, Paul B.
Weng, Connie C. Y.
Matin, Angabin
Meistrich, Marvin L.
Fetal Radiation Exposure Induces Testicular Cancer in Genetically Susceptible Mice
title Fetal Radiation Exposure Induces Testicular Cancer in Genetically Susceptible Mice
title_full Fetal Radiation Exposure Induces Testicular Cancer in Genetically Susceptible Mice
title_fullStr Fetal Radiation Exposure Induces Testicular Cancer in Genetically Susceptible Mice
title_full_unstemmed Fetal Radiation Exposure Induces Testicular Cancer in Genetically Susceptible Mice
title_short Fetal Radiation Exposure Induces Testicular Cancer in Genetically Susceptible Mice
title_sort fetal radiation exposure induces testicular cancer in genetically susceptible mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278464/
https://www.ncbi.nlm.nih.gov/pubmed/22348147
http://dx.doi.org/10.1371/journal.pone.0032064
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