Eric W. Hahn

Aspermia and Recovery of Spermatogenesis in Cancer Patients Following Incidental Gonadal Irradiation during Treatment: A Progress Report

The 11 patients in this study who received incidental gonadal irradiation from clinical therapy all became aspermic within 8-34 weeks following treatment. The estimated gonadal dose was 118-228 rads. Five of these patients have shown recovery of spermatogenesis; 3 of these have reached fertilizable concentrations. Recovery of semen sperm was noted at 44-77 weeks following treatment. The other 2 patients, after 110-176 weeks, have sub-fertile concentrations of semen sperm. Five patients have not been followed for a sufficient length of time to permit recovery to be noted.

Differential Sensitivity of Three Sublines of the Rat Dunning Prostate Tumor System R3327 to Radiation and/or Local Tumor Hyperthermia

To better understand the relationship of the growth characteristics of tumor tissues and their response to ionizing radiation alone and in combination with local tumor hyperthermia, we compared three different tumor sublines of the Dunning rat prostate carcinoma R3327. This report includes results obtained with the anaplastic AT1 subline (volume doubling time 5.2 days), the moderately differentiated mucin-secreting HI subline (volume doubling time about 9 days) and the well-differentiated, hormone-dependent H subline (volume doubling time about 17 days). The effects of single doses of photons (10 to 40 Gy) with and without local tumor hyperthermia (35 min immersion at 43.5 degrees C) were quantified by growth delay. The time to reach five times the volume at the time of treatment after 30 Gy alone was found to be 56.0, 134.9 and 184.0 days for the R3327-AT1, HI and H tumors, respectively. The R3327-H tumor was more radiosensitive than the AT1 or HI subline. Five of nine R3327-H tumors were controlled locally with a single dose of photons (40 Gy). Local tumor hyperthermia alone induced growth delay in both differentiated tumors, while the anaplastic tumor subline did not respond. Combined treatment modalities with heat applied directly after irradiation revealed isoeffective thermal enhancement ratios for 30 Gy which decreased from 1.59 for the AT1 tumor and 1.42 for the HI tumor to 1.23 in the well-differentiated subline R3327-H.

Response of the Rat Dunning R3327-AT1 Prostate Tumor to Treatment with Fractionated Fast Neutrons

Reports indicate that cancer of the prostate, soft tissue sarcomas, salivary gland tumors, and melanomas respond well to fast-neutron treatment. To better understand the action of fast neutrons on such tumor tissues, we have begun studies with the versatile Dunning rat prostate tumor system. In our initial studies with the R3327-AT1 subline we observed a relative biological effectiveness (RBE) of approximately 3 for single doses of 14-meV fast neutrons. As a continuation of those studies the present report discusses our findings following fractionated treatments with 10 equal fractions of 14-MeV fast neutrons or 60Co gamma rays at several dose levels per fraction. After either fractionated neutron or photon treatment the volume of the tumors continued to increase for 2 weeks and then reached a plateau, the level of which was dose dependent. Tumor growth resumed and no local control was observed. Analysis of the data using growth delay as biological end point yielded an RBE of approximately 4.2 +/- 1.3.

Increased Litter Size in the Rat X-Irradiated during the Estrous Cycle before Mating

Average numbers of ovulations, implantations, and living fetuses obtained from rats x-irradiated during the estrous cycle before mating are a function of both the radiation dose and the time of exposure during the cycle. Animals irradiated during metestrus or the day thereafter exhibit significant increases in the factors studied, while those irradiated on the 3rd day after metestrus maintain fewer implantations after exposure to 300, 500, and 600 roentgens, and fewer living fetuses after exposure to 100 to 600 roentgens.

Effects of Social Environment on Mortality to Whole Body X-Irradiation in the Rat

Group- and individually-reared rats were exposed to 750 r of whole body x-irradiation and then subdivided into group- and individually-housed samples. There were no differential effects of housing on mortality rate among males. Among females there was an apparent interaction between the pre- and post-irradiation conditions of housing such that for the group-reared females there was a significantly greater mortality rate in the animals housed in groups than in those housed individually.

Abscopal delay of embryonic development after prefertilization x irradiation

In order to assess possible maternal effects of prefertilization x-irradiation on the development of embryos, Long-Evans rats in metestrus were exposed to 0, 200, or 400 R with concomitant shieldin...

Growth-State-Dependent Radiation-Induced Expression of the Proto-oncogene c-fos in NIH 3T3 Cells

Expression of the proto-oncogene c-fos in response to ionizing radiation has been observed in some but not all cell lines tested. Here we report on delayed, transient c-fos expression in NIH 3T3 cells induced by 60Co gamma rays in the dose range 2-5 Gy. Induction of c-fos was significantly increased in cells irradiated in the density-arrested quiescent state compared to irradiation in the exponential growth phase. The enhancement correlated with the transition to quiescence as measured by the proliferation markers, proliferating cell nuclear antigen and bromodeoxyuridine. The observation of growth-state-dependent expression of c-fos after irradiation might indicate a functional relationship between c-fos and growth control in the DNA damage response, e.g. a potential role of c-fos in the control of replicative proteins.

Postconception development of rat ova following X-ray induced superovulation

Prefertilization x-irradiation of Long-Evans rats induces an exposure dependent increase in ovulations, implantations and live term fetuses. However, the pre- and postimplantation losses are also dependent on the level of radiation. The early development of superovulated ova, induced by x-irradiation, was examined to elucidate the nature of pre- and postimplantation losses. Long-Evans rats were given 0, 200 and 400 R x-irradiation 4 days before mating. Ova were examined microscopically on days 0.5 and 3.5 of pregnancy. Corpora lutea, implantations and live term fetuses were examined on day 20.5 of pregnancy. After 400 R, fertilization is decreased. After 200 and 400 R, there was an increased degeneration of tubal embryos at day 3.5 of pregnancy. These factors may account for the preimplantation losses, however, another factor involved may be the formation of corpora lutea from unovulated follicles. Radiation also induced a significant mitotic delay in tubal embryos. Both the number of embryos delayed and ...

Increased Embryonic Survival in Irradiated Rats Receiving Progesterone Therapy

Average numbers of living fetuses in female rats exposed to 300 R of whole-body X-irradiation on the morning prior to mating were significantly (p≤ 0.05) increased following administration of 1.0 mg of progesterone (sc) on the afternoon prior to mating, by 7.5 mg of progesterone (sc) on days 7 to 12 of pregnancy, or by a combination of the above therapies. Possible mechanisms of action are discussed. The data are interpreted as evidence that radiation-induced maternal dysfunction is the contributing factor in a portion of the embryonic mortality observed in rats irradiated shortly before mating.

The Modification of

X-irradiation and housing regimen significantly reduced the uptake of T-3 by the red blood cells of the rat. Each treatment reduces the uptake by approximately 10%, and the effects are additive.