Frequency of minisatellite repeat number changes at the MS205 locus in human sperm before and after cancer chemotherapy

To determine whether the measurement of repeat number mutations at a minisatellite locus could detect human germline mutations induced by chemotherapy, we performed a longitudinal study of the mutation frequencies in sperm from 10 patients treated for Hodgkin's disease. Polymerase chain reactio...

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Bibliographic Details
Published in:Environmental and molecular mutagenesis 2000, Vol.36 (2), p.134-145
Main Authors: Zheng, Ningjia, Monckton, Darren G., Wilson, Gene, Hagemeister, Fredrick, Chakraborty, Ranajit, Connor, Thomas H., Siciliano, Michael J., Meistrich, Marvin L.
Format: Article
Language:English
Subjects:
Adult
Antineoplastic Combined Chemotherapy Protocols - adverse effects
Biological and medical sciences
Blood Cells - drug effects
chemotherapy
Cytoxan
dacarbazine
Drug toxicity and drugs side effects treatment
germline mutation
Hodgkin Disease - blood
Hodgkin Disease - drug therapy
human
Humans
lomustine
Male
mechlorethamine
Medical sciences
Microsatellite Repeats - drug effects
minisatellite
Miscellaneous (drug allergy, mutagens, teratogens...)
MS205 gene
Mutation
Novantrone
Oncovin
Pharmacology. Drug treatments
Polymerase Chain Reaction - methods
prednisone
procarbazine
Sarcoma - drug therapy
sperm
Spermatozoa - drug effects
Spermatozoa - physiology
Synovial Membrane
Time Factors
Citations: Items that this one cites
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Summary:To determine whether the measurement of repeat number mutations at a minisatellite locus could detect human germline mutations induced by chemotherapy, we performed a longitudinal study of the mutation frequencies in sperm from 10 patients treated for Hodgkin's disease. Polymerase chain reaction on small pools of DNA equivalent to 100 sperm and Southern blotting were used to screen at least 7900 sperm in each sample to quantify the mutation frequency at the minisatellite MS205 locus. Pretreatment and posttreatment semen samples were obtained at least 2 months after completion of therapy from 4 patients treated with a regimen (Novantrone, Oncovin, vinblastine and prednisone [NOVP]) that lacks alkylating agents and from three patients treated with regimens (Cytoxan, vinblastine, procarbazine and prednisone/Adriamycin, bleomycin, dacarbazine, lomustine, and prednisone [CVPP/ABDIC] or mechlorethamine, Oncovin, procarbazine and prednisone [MOPP]) containing alkylating agents. There were no effects of NOVP or CVPP/ABDIC on the mutation frequencies. In the 1 patient treated with MOPP, the treatment with the highest dose of gonadotoxic alkylating agents, there was a statistically significant increase in mutation frequency from 0.79% pretreatment to 1.14% posttreatment, indicating induction of mutations in stem spermatogonia. During‐treatment semen samples obtained from 2 patients treated with ABVD, which does not contain gonadotoxic alkylating agents, and 1 with NOVP also did not show any increases above the baseline mutation frequencies, indicating no increase in the minisatellite mutation frequency in spermatocytes. Thus, measurement of repeat number changes at minisatellite MS205 appears to be able to detect induced germline mutations in human sperm. However, most chemotherapy regimens do not significantly increase this class of mutations. Environ. Mol. Mutagen. 36:134–145, 2000. © 2000 Wiley‐Liss, Inc.
ISSN:0893-6692
1098-2280
DOI:10.1002/1098-2280(2000)36:2<134::AID-EM8>3.0.CO;2-D