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X-ray induced mutation in Syrian hamster fetal cells
Paul J Donovan1, George T Smith
1Laboratory of Comparative Carcinogenesis, Department of Health and Human Services, National Cancer Institute at Frederick, Building 538, Room 205E, Frederick, MD 21702-1201, USA. donovapa@mail.ncifcrf.gov
Mutation Research
|March 14, 2002
Summary
Fetal cells are highly sensitive to X-ray induced mutations. Even low doses of radiation significantly increase mutation frequency, suggesting a potential link to childhood cancer risk.
Area of Science:
- Radiation biology
- Developmental toxicology
- Cancer genetics
Background:
- Transabdominal X-rays are a known risk factor for childhood leukemia.
- Fetal exposure to X-rays in mice has shown increased mutations and tumors in offspring.
- Quantitative data on fetal sensitivity and dose-response for X-ray mutagenesis is lacking.
Purpose of the Study:
- To quantify fetal sensitivity to X-ray-induced mutagenesis.
- To determine the dose-response relationship for transplacental X-ray mutagenesis.
- To assess the potential contribution of fetal mutations to childhood cancer risk.
Main Methods:
- Pregnant Syrian hamsters at day 12 of gestation were exposed to 300-kV X-rays.
- Fetal cells were harvested 24 hours post-irradiation for a 5-day culture period.
- Mutation frequency was assessed using 6-thioguanine (6-TG) selection and colony formation assays.
Main Results:
- Mutation frequency showed a linear response across the 10-600 R dose range.
- The average induced 6-thioguanine mutant frequency was 4.7 x 10(-7) per R.
- A 10 R dose resulted in a 2.5-fold increase in mutation frequency per R, consistent with epidemiological data.
Conclusions:
- Fetal cells exhibit high sensitivity to X-ray-induced mutations.
- A no-effect threshold for transplacental X-ray mutagenesis is unlikely.
- These findings support the hypothesis that X-ray-induced fetal mutations contribute to the increased risk of childhood cancer.