Tomoko Kusama

Radiotherapy during pregnancy : Effects on fetuses and neonates

To optimize the efficacy of radiotherapy for cancer patients who are pregnant, the following factors must be considered: the potential effects of the therapy on fetuses and neonates, the stage and prognosis of the mothers disease, and the possible risks to the patient of restricting cancer treatment. Malformations and mental retardation are the most serious consequences of fetal exposure to radiation that are observed after birth. The sensitivity to radiation is high from 2 to 8 weeks after conception for malformations and from 8 to 25 weeks (particularly up to week 15) for mental retardation; the risk of mental retardation declines rapidly after the 25th week of gestation. When a pregnant patient requires radiation therapy, the physician should consider fetal sensitivity to radiation in light of gestational age and the expected dose of radiation and should then calculate the risk to the fetus versus the benefits to the mother. The risk is negligible if fetal exposure does not exceed 0.1 Gy, preferably remaining below 0.05 Gy, during gestation. Furthermore, it is safest to administer radiotherapy during or after the 25th week of gestation.

The Embryonic and Fetal Effects in ICR Mice Irradiated in the Various Stages of the Preimplantation Period

Pregnant ICR mice were irradiated with 0.1-2.5 Gy 137Cs gamma rays at a dose rate of 0.2 Gy/min at 2, 48, 72 or 96 h postconception. In the mice irradiated during these stages of preimplantation, embryonic/fetal mortalities, incidence of external gross malformations, fetal body weight and sex ratio were observed at day 18 of gestation. There were significant increases in death in the preimplantation period compared to control levels after exposure to at least 0.25 Gy at 2 and 72 h postconception and 0.5 Gy at 96 h postconception. In contrast, a dose of 1.5 Gy was required at 48 h postconception. The frequency of embryonic death was analyzed using a logistic regression for comparing among stages. These analyses demonstrated that the regression slopes were significantly positive for groups in all stages and increased with decreasing time after conception. Furthermore, the regression analyses suggested that the most sensitive stage for preimplantation death and embryonic death was 2 h postconception, when embryos consisted of one cell. Many types of external gross malformations, such as exencephaly, cleft palate and anophthalmia, were observed even in the mice irradiated with 0.1 Gy at 2, 72 and 96 h postconception. In the same manner as embryonic mortality, the regression analyses suggested that the susceptibility of the mice irradiated at 2, 72 and 96 h postconception during preimplantation to external malformations was higher than that of the mice irradiated at 8 or 11 days of gestation, which is the period of organogenesis, and that the most sensitive stage for external malformations was 2 h postconception. However, no malformations were observed in the mice irradiated at 48 h postconception when the embryos were precompacted with four to eight cells.

Combined effects of radiation and caffeine on embryonic development in mice

The combined effect of radiation and caffeine has been studied in mouse embryos. Radiation and/or caffeine were administered to ICR mice on Day 11 of gestation. Intrauterine death, gross malformation, and fetal body weight were selected as indicators of effects. Doses of whole-body gamma irradiation were 0.5 to 2.5 Gy and those of caffeine were 100 and 250 mg/kg maternal body wt. Intrauterine mortality increased with increasing radiation dose; this trend was more remarkable in combination with caffeine. Gross malformations such as cleft palate and defects of forelegs and hindlegs appeared frequently in the fetuses treated with both radiation and caffeine. Decreased fetal weight was observed even in mice treated with 0.5 Gy of radiation or 100 mg/kg caffeine. There was a linear relationship between dose and reduction of fetal weight. The fetal weight was a sensitive, precise, and easy-to-handle indicator for the effects of growth retardation. Intrauterine mortality and frequencies of cleft palate and defects of forelegs and hindlegs were higher than the sum of those induced by radiation and by caffeine separately. The results indicated that the combined action of radiation and caffeine on intrauterine death and malformations was synergistic.

Stage Differences in Developmental Disorders in ICR Mouse Embryos Irradiated with Gamma-Rays

This study was designed to determine precisely the radiosensitive period in the development of ICR mouse embryos during which external malformations and growth retardation tend to occur. Female and male mice were placed together for only three hours to allow fairly precise identification of the time of conception. The pregnant mice were divided into 31 groups, which were irradiated in turn with 1.5 Gy gamma radiation at 6‐hour intervals during the period of organogenesis. They were then observed on day 18 of gestation. Items recorded were intrauterine death, external malformations, sex ratio and fetal body weight. Death of the embryo/fetus, especially death in the early period of organogenesis, was most frequent in mice irradiated between days 6.75 and 8.25 of gestation, but there was no statistically significant difference in the frequency of early‐ and late‐period deaths between irradiated and control groups. The types and frequencies of external malformations observed differed according to the exposure period. The most highly sensitive period for each malformation lasted no more than 12 hours. Reduction of fetal body weight was a good indicator of radiation effects, and was observed mostly in the groups irradiated between days 9.75 and 11.00 of gestation. The sex ratio was not affected by the period in which irradiation was performed.

The Whole-Body (Human) Counter of the University of Tokyo: Its Structure and Performance

A description is given of the design and performance of a whole-body counter at the University of Tokyo. The apparatus is intended for use in medical research and as control measure for radiation protection. Three types of detectors are installed for whole body counting of the human subject: (a) 5″ Nal(Tl) scintillation probe, (b) 2.5″ Nal(Tl) scintillation probes, and (c) large plastic scintillation probes. Output signals from the detectors are analyzed in a 400-channel pulse height analyzer. The subject is measured either on: (a) stretcher, (b) chair, or (c) V-bottom bed. In using the plastic scintillation probes, counting for a period of 15 min suffices to detect 150 g of potassium in the body, allowing for a statistical counting error of 2.2%. Spectra from some human subjects are presented.

The Whole-Body (Human) Counter of the University of Tokyo

A description is given of the design and performance of a whole-body counter at the University of Tokyo. The apparatus is intended for use in medical research and as control measure for radiation protection. Three types of detectors are installed for whole body counting of the human subject: (a) 5″ Nal(Tl) scintillation probe, (b) 2.5″ Nal(Tl) scintillation probes, and (c) large plastic scintillation probes. Output signals from the detectors are analyzed in a 400-channel pulse height analyzer. The subject is measured either on: (a) stretcher, (b) chair, or (c) V-bottom bed. In using the plastic scintillation probes, counting for a period of 15 min suffices to detect 150 g of potassium in the body, allowing for a statistical counting error of 2.2%. Spectra from some human subjects are presented.