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
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