Meiotic susceptibility for induction of sperm with chromosomal aberrations in patients receiving combination chemotherapy for Hodgkin lymphoma


Por: Frias, Sara, Van Hummelen, Paul, Meistrich, Marvin L., Wyrobek, Andrew J.

Publicada: 28 dic 2020
Categoría: Multidisciplinary

Resumen:
Improvements in survival rates with gonad-sparing protocols for childhood and adolescence cancer have increased the optimism of survivors to become parents after treatment. Findings in rodents indicate that chromosomal aberrations can be induced in male germ cells by genotoxic exposures and transmitted to offspring and future generations with effects on development, fertility and health. Thus, there is a need for effective technologies to identify human sperm carrying chromosomal aberrations to assess the germ-line risks, especially for cancer survivors who have received genotoxic therapies. The time-dependent changes in the burden of sperm carrying structural chromosomal aberrations were assessed for the first time in a cancer setting, using the AM8 sperm FISH protocol which simultaneously detects abnormalities in chromosomal structure and number in sperm. Nine Hodgkin lymphoma (HL) patients provided 20 semen samples before, during, and after NOVP therapy (Novantrone, Oncovin, Velban and Prednisone) and radiation therapy that produced scattered gonadal doses from <0.05 to 0.6 Gy. Late meiosis was found to be the most sensitive to NOVP treatment for the production of sperm with chromosomal abnormalities, both in structure and number. Earlier stages of spermatogenesis were less sensitive and there was no evidence that therapy-exposed stem cells resulted in increased frequencies of sperm with abnormalities in chromosomal structure or number. This indicates that NOVP therapy may increase the risks for paternal transmission of chromosomal structural aberrations for sperm produced 32 to 45 days after a treatment with these drugs and implies that there are no excess risks for pregnancies conceived more than 6 months after this therapy. This clinical evaluation of the AM8 sperm FISH protocol indicates that it is a promising tool for assessing an individual's burden of sperm carrying chromosomal structural aberrations as well as aneuploidies after cancer therapy, with broad applications in other clinical and environmental situations that may pose aneugenic or clastogenic risks to human spermatogenesis.

Filiaciones:
Frias, Sara:
 Lawrence Livermore Natl Lab, Hlth Effects Genet Div, Livermore, CA 94550 USA

 Univ Nacl Autonoma Mexico, Inst Invest Biomed, Inst Nacl Pediat, Lab Citogenet, Mexico City, DF, Mexico

Van Hummelen, Paul:
 Lawrence Livermore Natl Lab, Hlth Effects Genet Div, Livermore, CA 94550 USA

 Stanford Univ, Dept Med, Palo Alto, CA 94304 USA

Meistrich, Marvin L.:
 Univ Texas MD Anderson Canc Ctr, Dept Expt Radiat Oncol, Houston, TX 77030 USA

Wyrobek, Andrew J.:
 Lawrence Livermore Natl Lab, Hlth Effects Genet Div, Livermore, CA 94550 USA

 Lawrence Berkeley Natl Lab, Biol Syst & Engn Div, Berkeley, CA 94720 USA
ISSN: 19326203





PLOS ONE
Editorial
PUBLIC LIBRARY SCIENCE, 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA, Estados Unidos America
Tipo de documento: Article
Volumen: 15 Número: 12
Páginas:
WOS Id: 000603611900007
ID de PubMed: 33370316

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