ArticleProceedings of the National Academy of Sciences of the United States of America2012
Exposure to anticancer drugs can result in transgenerational genomic instability in mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 77 citations in OpenAlex.
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- A view on drug resistance in cancer.Nature · 2019Review
- Mutation Induction in Humans and Mice: Where Are We Now?Cancers · 2019Review
- Non-oncologic Indications for Male Fertility Preservation.Current urology reports · 2019Review
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- Peri-tumor administration of 5-fluorouracil sol-gel using a hollow microneedle for treatment of gastric cancer.Drug delivery · 2018Article
- Perturbation of microRNA signalling by doxorubicin in spermatogonial, Leydig and Sertoli cell linesToxicology research · 2018Article
- Loss of PUMA protects the ovarian reserve during DNA-damaging chemotherapy and preserves fertility.Cell death & disease · 2018Article
- Carnosine attenuates cyclophosphamide-induced bone marrow suppression by reducing oxidative DNA damage.Redox biology · 2018Article
- Adverse effects of paternal chemotherapy exposure on the progeny brain: intergenerational chemobrain.Oncotarget · 2018Article
- Protective Effects of Fullerene COxidative medicine and cellular longevity · 2018Article
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- Medullary thyroid cancer, leukemia, mesothelioma and meningioma associated with germline APC and RASAL1 variants: a new syndrome?Hormones (Athens, Greece) · 2017Article
- Amelioration of the cyclophosphamide induced genotoxic damage in mice by the ethanolic extract ofToxicology reports · 2017Article
- Perturbation of epigenetic processes by doxorubicin in the mouse testis.Toxicology research · 2016Article
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
Abstract
The genetic effects of human exposure to anticancer drugs remain poorly understood. To establish whether exposure to anticancer drugs can result not only in mutation induction in the germ line of treated animals, but also in altered mutation rates in their offspring, we evaluated mutation rates in the offspring of male mice treated with three commonly used chemotherapeutic agents: cyclophosphamide, mitomycin C, and procarbazine. The doses of paternal exposure were approximately equivalent to those used clinically. Using single-molecule PCR, the frequency of mutation at the mouse expanded simple tandem repeat locus Ms6-hm was established in DNA samples extracted from sperm and bone marrow of the offspring of treated males. After paternal exposure to any one of these three drugs, expanded simple tandem repeat mutation frequencies were significantly elevated in the germ line (sperm) and bone marrow of their offspring. This observed transgenerational instability was attributed to elevated mutation rates at the alleles derived from both the exposed fathers and from the nonexposed mothers, thus implying a genome-wide destabilization. Our results suggest that paternal exposure to a wide variety of mutagens can result in transgenerational instability manifesting in their offspring. Our data also raise important issues concerning delayed transgenerational effects in the children of survivors of anticancer therapy.
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