Unchanged cardiovascular and respiratory outcomes in healthy C57Bl/6 mice after in utero exposure to ionizing radiation.

BACKGROUND: Advancements in medical technologies that utilize ionizing radiation have led to improved diagnosis and patient outcomes, however, the effect of ionizing radiation on the patient is still debated. In the case of pregnancy, the potential effects are not only to the mother but also to the fetus. The aim of this study was to determine if exposure from ionizing radiation during pregnancy alters the development of the cardiovascular and respiratory system of the offspring. MATERIALS AND METHODS: Pregnant C57Bl/6 mice were whole-body irradiated at gestational day 15 with a 137Cs gamma radiation emitting source at 0 mGy (sham), 50 mGy, 300 mGy, or 1000 mGy. Post weaning weight and blood pressure measurements were taken weekly for both male and female pups until euthanasia at 16-17 weeks postnatal age. Immediately following, the trachea was cannulated, and the lungs and heart excised. The lung was then examined to assess respiratory physiological outcomes. RESULTS AND CONCLUSIONS: In utero exposures to 1000 mGy caused significant growth reduction compared to sham irradiated, which remained persistent for both male and female pups. Growth restriction was not observed for lower exposures. There was no significant change in any cardiovascular or respiratory outcomes measured. Overall, intrauterine exposures to ionizing radiation does not appear to significantly alter the development of the cardiovascular and respiratory system in C57Bl/6 pups up to 17 weeks postnatal age.

Cardiovascular and growth outcomes of C57Bl/6J mice offspring exposed to maternal stress and ionizing radiation during pregnancy.

Purpose: Developmental programming involves an adverse intrauterine environment which can result in offspring phenotype changes following birth. The developmental programming of hypertension has been reported to possibly involve oxidative stress at the cellular level. Ionizing radiation produces oxidative stress, even at low doses, and irradiation of animals is often coupled with potential sources of maternal stress such as transportation of animals or repeated handling. Materials and methods: Pregnant C57Bl/6J mice were irradiated on gestational day 15 with 5-1000 mGy 137Cs gamma radiation. Post-natal weight, blood pressure (BP) and heart rate (HR) were measured. Radiation had minimal effects at doses ≤300 mGy, but 1000 mGy caused a significant reduction in HR in male pups and growth reduction at 16 weeks of age in both genders. The sham-irradiation protocol included repeated transportation in order to acclimate animals to transport. However, it may have resulted in programming, as sham-irradiation alone resulted in elevated BP measures compared to the offspring of animals that were never transported. Results and conclusions: Overall, there were minimal effects on cardiovascular measures or offspring weight due to irradiation except at 1000 mGy. The presence of maternal stress, a known trigger of developmental programming, may have confounded any potential irradiation effects.

CYP3C gene regulation by the aryl hydrocarbon and estrogen receptors in zebrafish.

Cytochrome P450 (CYPs) enzymes are critical for the metabolism of exogenous and endogenous compounds. In mammals, the CYP3s are arguably the most important xenobiotic metabolizing enzymes and are all contained within the CYP3A subfamily. In fish, CYP3s include CYP3A and multiple subfamilies unique to the teleost lineage. The goal of this study was to provide insight on the regulation of genes in the CYP3C subfamily. Zebrafish, which have 4 CYP3C genes, were exposed to 17ß-estradiol (E2; 0.001-10 µM) or ß-naphthoflavone (ßNF; 0.005-1 µM), prototypical ligands of the estrogen receptor (ER) and the aryl hydrocarbon receptor (AhR), respectively. Gene expression was measured in the liver, intestine and gonads using quantitative PCR. CYP1A and vitellogenin (VTG) gene expression were used as positive controls for AhR and ER regulation, respectively. Exposure to ßNF resulted in the dose-dependant induction of CYP1A and CYP3C genes in the female intestine but not in the liver. E2 exposure resulted in the induction of all CYP3Cs in the male intestine and in the female liver. VTG was induced in both female and male livers. CYP3C3 and CYP3C4 were induced in the testis; CYP3C1 and CYP3C4 were slightly induced in the ovary. The time-course of gene induction was investigated in the liver and intestine after exposure to ßNF (0.5 µM) and E2 (0.1 µM). Inducible genes were up-regulated within 12 h after exposure. These data support a role for the AhR and ER in the regulation of CYP3Cs. Overall, the induction of CYP3Cs by AhR and ER ligands is different from mammalian CYP3A and may suggest a functional role for CYP3Cs that involves planar aromatic hydrocarbons and steroids.

Ionizing Radiation Exposure During Pregnancy: Effects on Postnatal Development and Life.

Reliable human data on the effects of prenatal exposure to ionizing radiation are largely based on high-dose exposures. Exposure to low doses may produce effects that are not easily observable at birth, and may persist over the course of the offspring's postnatal life. This is important when considering fetal programing, a phenomenon characterized by changes in offspring phenotype due to a stress experienced in utero. In this review, we briefly summarize the known effects of both high- and low-dose exposure to ionizing radiation during pregnancy in humans. There is a major consensus that the atomic bomb survivors' data shows increased incidence of microcephaly and reductions in IQ of A-bomb survivors, whereas, with diagnostic radiography in utero there is no conclusive evidence of increased cancer risk. Due to the relatively limited data (particularly for low-dose exposures) in humans, animal models have emerged as an important tool to study prenatal effects of radiation. These animal models enable researchers to manipulate various experimental parameters and make it possible to analyze a wider variety of end points. In this review, we discuss the major findings from studies using mouse and rat models to examine prenatal ionizing radiation effects in postnatal development of the offspring. In addition, we broadly categorize trends across studies within three major stages of development: pre-implantation, organogenesis and fetal development. Overall, long-term effects of prenatal radiation exposure (including the possible role on the developmental programing of disease) are important factors to consider when assessing radiation risk, since these effects are of relevance even in the low-dose range.