Chemotherapy induces transient sex chromosomal and autosomal aneuploidy in human sperm.
Each year more than 20,000 children and young persons of reproductive age are exposed to known mutagens in the form of chemo- and/or radiotherapy for cancer in the States. As more of these treatments are effective there is growing concern that genetic defects are introduced in the germ cells of these young patients. It is well documented for male rodents that treatment with chemo- and radio-therapeutic agents before mating can cause genetic damage in the germ line, and the magnitude of heritable effects depends on the spermatogenic cell stage treated. Similar germinal effects are suspected to occur in humans but remain unproven. Hodgkin's disease (HD) is an example of a malignancy which is typically diagnosed during a patient's reproductive years. In our study we observed eight male HD patients who were treated with NOVP (Novanthrone, Oncovin, Vinblastine, Prednisone) chemotherapy. We evaluated sperm aneuploidy using multi-colour fluorescence in situ hybridization (FISH), and found approximately 5-fold increases in sperm with disomies, diploidies and complex genotypes involving chromosome X, Y and 8. Increases in sex chromosome aneuploidies arose from segregation errors at meiosis I as well as meiosis II. The aneuploidy effects were transient, however, declining to pretreatment levels within approximately 100 days after the end of the therapy. When compared with normal men, some HD patients showed higher proportions of certain sperm aneuploidy types even before their first therapy.
Robbins
W A
WA
Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, Livermore, California 94551, USA.
Meistrich
M L
ML
Moore
D
D
Hagemeister
F B
FB
Weier
H U
HU
Cassel
M J
MJ
Wilson
G
G
Eskenazi
B
B
Wyrobek
A J
AJ
D000328:Adult; D000782:Aneuploidy; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004171:Diploidy; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000235:genetics* / Q000532:radiotherapy; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use; D012016:Reference Values; D013094:Spermatozoa / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D014747:Vinblastine / Q000009:adverse effects / Q000627:therapeutic use; D014750:Vincristine / Q000009:adverse effects / Q000627:therapeutic use
D000970:Antineoplastic Agents; D014750:Vincristine; D014747:Vinblastine; D011241:Prednisone