Jon B. Reitan

Relationship Between Intestinal Fibrosis and Histopathologic and Morphometric Changes in Consequential and Late Radiation Enteropathy

Intestinal fibrosis is a marked feature of late radiation enteropathy. This study assessed the time dose fractionation relationships of radiation-induced fibrosis in order to elucidate possible pathogenetic mechanisms. In 290 male Sprague-Dawley rats, a loop of small bowel was transposed to the left side of the scrotum. Three weeks later, the transposed segment was irradiated with either single dose or various fractionated regimens. The animals were observed for radiation-induced intestinal complications and killed in groups, 2 and 26 weeks after completion of irradiation. A semiquantitative histopathologic radiation injury score, morphometry of the submucosa, submucosal arterioles, intestinal surface area, and relative collagen content were used as endpoints. Fibrosis, measured by collagen assay and radiation injury score, increased with total dose, increasing fraction size and reduction in overall treatment time. This paralleled the results of morphometric assessment of mucosal surface area. Differences in vascular morphometry were only statistically significant in response to changes in total dose and fraction size and not with changes in overall treatment time. We conclude that fibrosis increases with increasing observation time, increasing fraction size, increasing total dose, and reduction of interfraction interval. Consequential injury, occurring as a result of disruption of mucosal integrity, seems to be an important mechanism for development of intestinal fibrosis. In contrast, vascular injury is relatively independent of this mechanism.

TOLERANCE OF RAT SMALL INTESTINE TO LOCALIZED SINGLE DOSE AND FRACTIONATED IRRADIATION

The tolerance of rat small intestine to localized single-dose and fractionated irradiation was assessed. In 168 rats, bilateral orchiectomy was performed and a loop of small intestine was transposed to the left part of the scrotum. Beginning 3 weeks postoperatively, single dose (18-24 Gy) or fractionated (4.2 Gy or 5.6 Gy per fraction) x-irradiation was delivered to the transposed intestine. The animals were observed for complications, and groups of animals were killed 2 and 26 weeks after completion of irradiation for assessment of injury. Mortality (i.e. the occurrence of lethal intestinal complications) and a semiquantitative histopathologic scoring system were used as endpoints to assess the degree of radiation injury. The most frequent intestinal complications were enterocutaneous fistula formation and intestinal obstruction. Logistic regression analysis ov complications data was used to estimate LD50 values and the alpha/beta ratio. There was good correlation between histopathologic scores and the incidence of lethal complications. The estimated LD50 values were 22.1 +/- 0.5 Gy, 37.0 +/- 4.4 Gy and 51.0 +/- 5.3 Gy for the single dose regimen and the fractionated regimens of 5.6 Gy and 4.2 Gy respectively. The estimated alpha/beta ratio was 10.7 +/- 2.4 Gy. The goodness of fit of the linear-quadratic isoeffect model to our data was satisfactory. Our results indicate that acute mucosal damage may be pathogenetically involved in the development of intestinal complications.

Hatching in zebrafish (Danio rerio) embryos exposed to a 50 Hz magnetic field.

Zebrafish embryos were exposed intra ovo to a 50 Hz AC magnetic field of 1000 microT rms, and the progress of asynchronous hatching was monitored. A statistically significant delay was observed when field exposure started 48 h after fertilization. In contrast, when exposure started 2 h after fertilization, no statistically significant effect was seen. When field exposure was administered together with submaximal doses of progesterone at 48 h postfertilization, the two treatments appeared to delay hatching in an additive manner. Evaluating the progress of hatching in zebrafish embryos seems relevant for exploration of EMF effects on reproduction.

Influence of interferon and radiation on serotonin content in primary carcinoid cell cultures.

Carcinoids are in general thought to be radioresistent, and have not been subjected to radiation therapy, except for palliative purposes. Clinical experience has indicated that interferons might enhance radiation effect and toxicity. In order to examine the effect of radiation, the combination of radiation and interferon, and the usefulness of the main metabolic product of primary cell cultures--serotonin--as a response indicator, we exposed primary carcinoid cell cultures with and without interferon pretreatment to radiation (2 Gy and 8 Gy). Irradiation alone had no effect on the serotonin content of the medium at the low dose (2 Gy) and even at the high dose (8 gy) the effect was not significant. When cells were preincubated with 1,000 IU/ml alpha-interferon, however, irradiation with 8 Gy induced a significant reduction of the hormone concentration in the medium on day 12 to 54.9 +/- 8.0% of the control value (p = 0.026). We think our model may provide a useful tool for further exploration of these mechanisms.

Airline Crew, Cosmic Radiation and Cancer. Status of the Current Norwegian Study and the Proposed European Study

Airline personnel are exposed to cosmic radiation to a varying degree, depending primarily upon flight altitude and the type of routes flown. The number of flight hours flown per year has been compiled on a person-by person basis for all pilots certified for commercial aviation in Norway since 1947. To a large extent the files also contain various information on type of aircraft flown, and employing air company for these pilots, and this information will be used to estimate the individual radiation histories. In the project described in the following, the intention is to link estimated radiation exposure histories of individual airline pilots with data from the Cancer Registry of Norway to reveal possible relationships between dose and health effects. There are firm plans for expanding this project to include a number of European countries. At present an intent to participate has been expressed from Denmark, Finland, Germany, Greece, Italy, Netherlands and Norway. Strong interest has also been expressed from France and Belgium.