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Title: Relative susceptibilities of male germ cells to genetic defects induced by cancer chemotherapies

Abstract

Some chemotherapy regimens include agents that are mutagenic or clastogenic in model systems. This raises concerns that cancer survivors, who were treated before or during their reproductive years, may be at increased risks for abnormal reproductive outcomes. However, the available data from offspring of cancer survivors are limited, representing diverse cancers, therapies, time-to-pregnancies, and reproductive outcomes. Rodent breeding data after paternal exposures to individual chemotherapeutic agents illustrate the complexity of factors that influence the risk for transmitted genetic damage including agent, dose, endpoint, and the germ-cell susceptibility profiles that vary across agents. Direct measurements of chromosomal abnormalities in sperm of mice and humans by sperm FISH have corroborated the differences in germ-cell susceptibilities. The available evidence suggests that the risk of producing chromosomally defective sperm is highest during the first few weeks after the end of chemotherapy, and decays with time. Thus, sperm samples provided immediately after the initiation of cancer therapies may contain treatment-induced genetic defects that will jeopardize the genetic health of offspring.

Authors:
; ;
Publication Date:
Research Org.:
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
875374
Report Number(s):
UCRL-JRNL-204915
Journal ID: ISSN 0198-0157; JNCIAM; TRN: US200603%%114
DOE Contract Number:  
W-7405-ENG-48
Resource Type:
Journal Article
Journal Name:
Journal of the National Cancer Institute
Additional Journal Information:
Journal Volume: 34; Journal ID: ISSN 0198-0157
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; BREEDING; CHEMOTHERAPY; DEFECTS; GENETICS; GERM CELLS; MALES; MICE; NEOPLASMS; PROGENY; RODENTS; SPERMATOZOA

Citation Formats

Wyrobek, A J, Schmid, T E, and Marchetti, F. Relative susceptibilities of male germ cells to genetic defects induced by cancer chemotherapies. United States: N. p., 2004. Web.
Wyrobek, A J, Schmid, T E, & Marchetti, F. Relative susceptibilities of male germ cells to genetic defects induced by cancer chemotherapies. United States.
Wyrobek, A J, Schmid, T E, and Marchetti, F. Tue . "Relative susceptibilities of male germ cells to genetic defects induced by cancer chemotherapies". United States. https://www.osti.gov/servlets/purl/875374.
@article{osti_875374,
title = {Relative susceptibilities of male germ cells to genetic defects induced by cancer chemotherapies},
author = {Wyrobek, A J and Schmid, T E and Marchetti, F},
abstractNote = {Some chemotherapy regimens include agents that are mutagenic or clastogenic in model systems. This raises concerns that cancer survivors, who were treated before or during their reproductive years, may be at increased risks for abnormal reproductive outcomes. However, the available data from offspring of cancer survivors are limited, representing diverse cancers, therapies, time-to-pregnancies, and reproductive outcomes. Rodent breeding data after paternal exposures to individual chemotherapeutic agents illustrate the complexity of factors that influence the risk for transmitted genetic damage including agent, dose, endpoint, and the germ-cell susceptibility profiles that vary across agents. Direct measurements of chromosomal abnormalities in sperm of mice and humans by sperm FISH have corroborated the differences in germ-cell susceptibilities. The available evidence suggests that the risk of producing chromosomally defective sperm is highest during the first few weeks after the end of chemotherapy, and decays with time. Thus, sperm samples provided immediately after the initiation of cancer therapies may contain treatment-induced genetic defects that will jeopardize the genetic health of offspring.},
doi = {},
journal = {Journal of the National Cancer Institute},
issn = {0198-0157},
number = ,
volume = 34,
place = {United States},
year = {2004},
month = {6}
}