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Transgenerational effects of preconception paternal contamination with (55)Fe
K P Hoyes1, B I Lord, C McCann
1Cancer Research Campaign Experimental Haematology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, M20 4BX, United Kingdom.
Radiation Research
|October 18, 2001
Summary
Paternal radiation exposure before conception can transmit cancer-predisposing genetic damage to offspring. Studies show (55)Fe irradiation in male mice led to increased leukemia in offspring when exposure occurred 84 days prior to mating.
Area of Science:
- Radiation biology
- Genetics
- Toxicology
Background:
- The link between paternal preconception radiation exposure and offspring cancer risk is debated.
- Previous studies indicate preconception irradiation can affect offspring hematopoiesis and carcinogen sensitivity.
Purpose of the Study:
- To investigate if preconception paternal exposure to the Auger electron emitter (55)Fe induces heritable damage predisposing offspring to cancer.
- To determine the impact of exposure timing (18 vs. 84 days before mating) on germline damage and offspring health.
Main Methods:
- Male DBA2 mice were injected with (55)Fe (4 kBq g(-1)) 18 or 84 days before mating.
- Sperm DNA integrity was assessed using comet analysis.
- Offspring were evaluated for bone marrow stem cell populations and challenged with methyl nitrosourea (MNU) to assess cancer incidence.
Main Results:
- Increased DNA strand breaks in sperm were observed 84 days after (55)Fe exposure, suggesting spermatogonial damage.
- Offspring from fathers exposed 84 days prior showed amplified bone marrow stem cell populations.
- Exposure to MNU significantly increased lympho-hemopoietic malignancies in offspring from the 84-day exposure group.
Conclusions:
- Paternal germline damage from (55)Fe irradiation can be transmitted to offspring.
- Damage to spermatogonia 84 days before conception increases offspring susceptibility to radiation-induced leukemogenesis.
- Findings support the hypothesis of heritable, potentially leukemogenic, genetic aberrations following paternal germline radiation exposure.