Life shortening in mice exposed to fission neutrons and gamma rays. VIII. Exposures to continuous gamma radiation

Data are presented on the mean aftersurvival of male B6CF1 mice exposed for 22 h per day, 5 days per week, to 60Co gamma radiation at dose rates of 1.36 to 12.64 x 10(-3) cGy/min for 23 weeks or 1.36 to 6.32 x 10(-3) cGy/min for 59 weeks. For deaths from all causes, linear dose-response curves were obtained with slopes (days of life lost/cGy) of 0.158 +/- 0.016 and 0.077 +/- 0.002 for 23- and 59-week exposures, respectively. These values were not significantly altered when the analysis was restricted to those mice dying with tumors (92% of the total) or to those presumably dying from tumors (82% of the total). Analysis of mortality rates showed that about 90% of the radiation-specific excess mortality was tumor related. The 59-week exposure series induced only a small increase in the number of days of life lost/cGy/weekly fraction over that induced by 23 weeks of irradiation, 4.53 +/- 0.15 compared to 3.64 +/- 0.36 days lost/cGy/weekly fraction. This lower than expected value for 59 weeks of exposure may signal the approach to the final linear, additive, injury term postulated from earlier studies at this laboratory with low-dose-rate, daily, duration-of-life 60Co gamma irradiation.     

Life shortening in mice exposed to fission neutrons and gamma rays. IV. Further studies with fractionated neutron exposures

When mice were exposed to a total dose of 240 rad of fission neutrons divided into two, four, or six fractions given at 1-week intervals, more life shortening was observed than was seen after a single exposure. Maximum life shortening was observed with four fractions, although the value for six fractions was not significantly lower. Much of the augmentation effect was attributable to an increase in early deaths during the first 200-300 days after exposure, although differences persisted throughout the lifetime of the animals. The changes in life shortening were associated with changes in the distribution of causes of death; however, decrementation of the populations for any given specific cause of death failed to eliminate completely the differences in mean aftersurvival time.     

Life shortening in mice exposed to fission neutrons and gamma rays. V. Further studies with single low doses

Data are presented on the mean after survival of female B6CF1 mice exposed to single doses of neutrons (1 to 40 rad) or gamma rays (22.5, 45, and 90 rad). For gamma-ray exposures and for neutron exposures up to 10 rad, the dose-response curves are indistinguishable from linear; higher neutron doses produce significant departures and linearity. Consequently, in these data, an upper limit of the relative biological effectiveness (RBE) exists for life shortening from all causes of death after single neutron exposures; this value is 15.0 +/- 5.1. The RBE depends on the cause of death, ranging from 2 to 5 for lymphoreticular tumors to 23-24 for lung tumors.     

Life shortening in mice exposed to fission neutrons and gamma rays. VII. Effects of 60 once-weekly exposures

A total of 6316 B6CF1 mice were exposed to 60 equal once-weekly doses of 0.85-MeV fission neutrons (0.033 to 0.67 cGy per weekly fraction) or 60Co gamma rays (1.67 to 10 cGy per weekly fraction) and were observed until they died. The mean aftersurvival times showed that the dose-response curves for both neutron and gamma-ray exposures were indistinguishable from linear over all doses except the highest neutron dose. The relative biological effectiveness (RBE) for neutrons, calculated as the ratio of the initial slopes of the dose-response curves, was about 20 for both males and females. Essentially the same value was obtained by a number of other analyses of the data. Virtually all of the radiation-specific excess mortality could be attributed to tumors; after decrementation of the population for nontumor deaths, the value of the RBE was not significantly changed.     

Preantral intra-ovarian oocyte release in the white-footed mouse,Peromyscus leucopus

Summary Optical diffraction analysis was carried out on crystalline inclusions in the rough endoplasmic reticulum of the insulin and somatostatin cells in the islet organ of the hagfish. A striking difference in crystalline arrangement was observed between the inclusions of the insulin and somatostatin cells. The crystallographic arrangement of the inclusions observed in situ in the insulin cells differed from that previously found by means of X-ray diffraction analyses of hagfish insulin crystals formed in vitro.     

Dichlorvos toxicity in the white-footed mouse (Peromyscus leucopus)

The organophosphate pesticide, dichlorvos (DDVP), is used commonly to control ectoparasites in laboratory rodents colonies. This compound is relatively nontoxic to Mus musculus at dosages several times the therapeutic level. However, usage of a similar therapeutic level in the white-footed mouse (Peromyscus leucopus) resulted in substantial mortality. To determine whether P. leucopus is more susceptible than M. musculus to the toxic effects of DDVP, both species were exposed to 0, 3 and 6 g of pelleted DDVP per cage. In a subsequent experiment, P. leucopus were exposed to 0 and 1 g of DDVP per cage. Mortality was not observed in M. musculus at any dosage level. P. leucopus exposed to 1, 3 and 6 g of DDVP exhibited mortalities of 3%, 20% and 53%, respectively. Mean serum cholinesterase in P. leucopus exposed to 3 and 6 g of DDVP was 0.35 and 0.21 U/ml as compared to 3.13 U/ml in unexposed mice. The analogous values for M. musculus were 1.60 and 0.79 U/ml while the level in unexposed mice was 6.79 U/ml. In the second experiment, mean serum cholinesterase in P. leucopus exposed to 1 g of DDVP was 0.32 U/ml as compared to 2.33 U/ml in unexposed mice. Histopathology revealed no lesions in the brain, liver or kidneys. The increased susceptibility of P. leucopus to the toxic effects of DDVP was related to the lowered serum cholinesterase. This indicates that DDVP should not be used for control of ectoparasites in P. leucopus.     

A possible mechanism of rapid luteolysis in white-footed mice,Peromyscus leucopus

Adult female white-footed mice, Peromyscus leucopus, were exposed to long (LP) or short (SP) photoperiods for 6 weeks (experiment I). Another group of animals was kept for 6 weeks in SP, then injected SC with 30 μg prolactin twice daily for 2, 3, 4, or 6 days (experiment II). Ovaries from the mice in both experiments were weighed and serially sectioned for light microscopic examination of regressing corpora lutea. In experiment I, it was observed that vessels supporting corpora lutea were dilated, and that their endothelium was either undergoing necrosis or it was missing. Pronounced changes of luteal capillaries led to rupture and intraluteal hemorrhage, thus opening the capillary bed. Regressing luteal cells became segregated and seemed to invade the vascular system passively. They were seen as luteal cell thrombi in medullary veins. This luteolytic course termed “rapid luteolysis” was most apparent in SP ovaries. It differed from “retarded luteolysis,” which represents the well-established luteolytic model of auto- and heterophagocytosis. In experiment II, there was a statistically significant decrease in ovarian weight 4 days after prolactin treatment in comparison with saline-treated controls. At the light microscopic level, signs of both rapid and retarded luteolysis were present, but not intensified. It is concluded: (1) The concept of rapid luteolysis represents a reasonable working hypothesis. (2) Prolactin, though luteolytic at the macroscopic level, failed to produce evidence of increased rapid or retarded luteolysis at the light microscopic level.     

Vasopressin and aggression in cross-fostered California mice (Peromyscus californicus) and white-footed mice (Peromyscus leucopus)

To examine how developmental experiences alter neural pathways associated with adult social behavior, we cross-fostered pups between the more aggressive and monogamous California mouse (Peromyscus californicus) and the less aggressive and polygamous white-footed mouse (P. leucopus). Cross-fostered males became more like their foster parents when tested as adults. Male white-footed mice became more aggressive only in an aggression test in a neutral arena, whereas the territorial California mice became less aggressive in resident-intruder aggression test, as measured by attack latency. Only the species that displayed a change in resident-intruder aggression showed a change in arginine vasopressin (AVP) levels: cross-fostered California mice had significantly lower levels of AVP-immunoreactive (AVP-ir) staining than controls in the bed nucleus of the stria terminalis (BNST) and the supraoptic nucleus (SON) and a nonsignificant trend toward lower levels in the medial amygdala (MA). Neither species showed changes in AVP-ir staining in a control area, the paraventricular nucleus (PVN). The changes in AVP-ir staining in the BNST and SON may not be caused by stress because cross-fostering was not associated with changes in adult plasma concentrations of two steroid hormones, corticosterone and testosterone, that have been associated with stress-related alterations in AVP pathways. These results suggest that manipulating the early parental environment can directly alter both a neurotransmitter system and species-typical patterns of social behavior, but that these effects may vary between species and under different social contexts.     

Myeloid leukemia in male RFM mice following irradiation with fission spectrum neutrons or gamma rays

The induction of myeloid leukemia following fission neutron irradiation was examined over the 0-80 rad dose range. Over this dose range the dose response could be described by the linear regression equation: y = 0.94 + 0.18X. A comparison of these data with data obtained following gamma irradiation from this study and a previous study indicated that the relative biological effectiveness for myeloid leukemia induction was 2.8. These results appear to be compatible with those reported by other investigators.     

Effect of long or short photoperiod on pineal melatonin content in the white-footed mouse,Peromyscus leucopus

Adult white-footed mice were maintained under either a long photoperiod (LP, LD 16:8, lights out at 2100) or a short photoperiod (SP, LD 8:16, lights out at 1700) for six weeks. Subgroups from each lighting regime were killed at specific times over a 24 hour period. Pineal radioimmunoassayable melatonin levels were significantly elevated at night compared to daytime values. Pineal melatonin content appears to be elevated for a longer period of time in the SP mice than in the LP animals. The apparent increased melatonin production observed in white-footed mice maintained under short and reproductively repressive daylengths may help to explain the ability of chronically available exogenous melatonin to cause gonadal atrophy in this species.     

Characteristics of a genetic polymorphism for reproductive photoresponsiveness in the white-footed mouse (Peromyscus leucopus)

Wild populations of Peromyscus are often composed of individuals that vary greatly in their reproductive response to photoperiod. A population of white-footed mice (P. leucopus) from Michigan (43 degrees N) was subjected to mass selection in the laboratory both for and against reproductive photoresponsiveness for four generations. The first generation of selection yielded one line of mice in which about 80% of the individuals were classified as reproductively photoresponsive (i.e., with undeveloped reproductive tracts when reared in short days, 8L: 16D) and another in which only about 20% were reproductively photoresponsive. Some and perhaps most of this difference was accounted for by changes in degree of responsiveness to photoperiod rather than by alterations in the proportion of discrete responsive vs. unresponsive phenotypes. Alteration of critical day length was not a factor. Three more generations of selection failed to change the proportions noted above significantly. Although the genetic control of reproductive photoresponsiveness is undoubtedly complex, a single variable locus may be responsible for much of the heritable variation present in this population. These results also suggest that natural populations contain genetically determined phenotypes that are intermediate between absolutely photoresponsive and absolutely unresponsive. The factors that might promote maintenance of heterogeneity of reproductive photoresponsiveness in a wild population of rodents are considered.