Radiation damage repair capacity of a human germ-cell tumour cell line: inhibition by 3-aminobenzamide

The capacity of a human germ-cell tumour line to repair radiation damage has been investigated by means of a clonogenic assay. Dose-rate dependence studies, split-dose experiments and experiments designed to measure repair of potentially lethal damage have been performed. The cells showed some ability to repair radiation-induced damage in all three types of experiment. An attempt has been made to understand the possible cellular mechanisms of these repair processes by the use of 3-aminobenzamide (3-AB), an agent thought to act by inhibition of ADP-ribosylation. 3-AB added 2 h prior to and removed 18 h after irradiation at a non-toxic dose to unirradiated cells caused a small but consistent increase in cell kill with acute (150 cGy min-1) irradiation, largely involving a reduction in the shoulder region of the survival curve, but had a greater effect in increasing cell kill at a dose rate of 7.6 cGy min-1 and an even greater effect at a dose rate of 1.6 cGy min-1. When 3-Ab was present 2 h prior to the first dose and between two equal doses in a split-dose experiment, inhibition of split-dose recovery was observed. In addition, some inhibition of potentially lethal damage recovery was observed with 3-AB. A possible role for poly(ADP-ribosylation) is thus implicated in the repair of radiation-induced damage of this human tumour cell line during continuous low dose rate or fractionated radiation schedules, although other effects of 3-AB on respiratory metabolism and/or purine synthesis cannot be eliminated as the cause of the observed inhibitory effects.     

Arachidonic acid and linoleic acid supplementation increase prostanoid production in rats fed a butter-enriched diet

Male Sprague Dawley rats were fed a butter-enriched diet (50% fat) for 2 weeks and then supplemented orally with either 90 mg of ethyl arachidonate or ethyl linoleate daily for 2 weeks. For comparative reasons, one group of animals was fed standard laboratory rat chow for 4 weeks. Aortic prostacyclin (PGI2) production, platelet aggregation and thromboxane A2 (TXA2) production and plasma and aortic phospholipid (PL) fatty acids were measured. When compared to butter-fed rats, aortic PGI2 production, collagen-induced platelet aggregation and TXA2 production were significantly increased in rats supplemented with ethyl arachidonate to levels similar to those seen in chow-fed rats. Ethyl linoleate supplementation also tended to increase aortic PGI2 production, collagen-induced platelet aggregation and TXA2, but not to the same extent. These changes were accompanied by increases in the level of arachidonic acid and linoleic acid in aortic and plasma PL and a decrease in the level of eicosapentaenoic acid (EPA) and docsahexaenoic acid (DHA). These data indicate that supplementation with small doses of preformed arachidonic acid was more effective than supplementation with its precursor, linoleic acid, in reversing the effects on prostanoid production and phospholipid fatty acid composition in rats fed diets enriched with butter.     

Protection of mice against mixed fission neutron-gamma (n: gamma = 1:1) irradiation by WR-2721, 16,16-dimethyl PGE2, and the combination of both agents

The survival of mice after whole-body exposure to a modified fission neutron-gamma field (n: gamma = 1:1) was used to examine radiation protection by WR-2721, 16,16-dimethyl PGE2(DiPGE2), and the combination of both agents. Administration of WR-2721 (453 mg/kg) increased the LD50/30 from 5.24 to 7.17 Gy (DMF = 1.37), whereas pretreatment with DiPGE2 (1.6 mg/kg) increased the LD50/30 to 5.77 Gy (dose modification factor (DMF) = 1.10). The combination of 453 mg/kg WR-2721 and 0.4 mg/kg DiPGE2 resulted in an LD50/30 of 7.33 Gy, yielding a DMF of 1.39. However, no significant difference in protection was obtained with the combination of the two agents compared to that seen with WR-2721 alone.     

Lung Cancer—Improved Cytologic Detection by Inducing Production of Sputum

The principle of producing bronchial lavage by deposition of large amounts of heated aerosol has resulted in a significantly greater yield of positive cytologic diagnosis of bronchogenic carcinoma than with repeated “volunteer” specimens of sputum. Positive pressure plus bronchodilators augments greater sputum volume.Using this technique, cases in which results of bronchoscopy and aspiration biopsy were negative for malignant change, were diagnosed cytologically.Application of this technique can sometimes detect early lung carcinoma before roentgenographic changes are detectable. Positive tests in clinically far advanced disease may prevent unnecessary surgical intervention.The simplicity of the technique, the freedom from adverse reactions, and its wide acceptance by the subjects tested, make it valuable in the diagnosis of lung cancer.     

Photoperiodic influences on sexual behavior in male Syrian hamsters

The effect of photoperiodic conditions on sexual behavior was investigated in male Syrian hamsters that were either gonadally intact, or castrated and treated with low doses of testosterone throughout the experiment. Hamsters were exposed to long (LD 16:8) or short (LD 8:16) days for 7 weeks; for the next 8 weeks, either they were exposed to an intermediate daylength (LD 12:12), or daylength conditions remained unchanged. Sexual behavior was affected by photoperiod conditions in both gonadally intact animals and testosterone-treated castrates, but to different degrees. Intact males exposed to short days for 15 weeks exhibited gonadal regression, and their copulatory performance was impaired. The percentage of animals that intromitted or ejaculated was significantly reduced. Additional measures of sexual performance among the copulating males were also affected. In contrast, among the castrates with testosterone clamped at low but stable levels, the proportion of males that mounted, intromitted, or ejaculated was not affected by photoperiod. However, among the males that continued to copulate, sexual performance changes were present in the short-day castrates that resembled those displayed by the intact males. We infer that these behavioral effects in both hormonal conditions reflect primarily a difficulty in the attainment of intromission. Gonadal regression alone cannot easily account for the behavioral deficits of the intact males, because circulating testosterone levels at the end of the experiment were not significantly different between the gonadally intact hamsters and the castrated, testosterone-treated hamsters exposed continuously to short days. Males transferred from either long or short days to the intermediate-daylength condition responded behaviorally to this photoperiod as if it were a short day, that is, their ejaculatory frequency declined. We conclude that male hamsters exposed to photoinhibitory daylengths exhibit deficits in their sexual behavior, not only because endogenous levels of testosterone decrease, but also because the substrates on which this hormone acts become less responsive. We hypothesize that under physiological conditions, the episodic secretion of testosterone imposes constraints on the maintenance or restoration of copulation, and that the potent behavioral effects achieved by constant-release implants of testosterone may mask the presence of photoperiodically induced alterations in the hamster's sensitivity to this gonadal hormone.     

Kinetic disposition of an aqueous formulation of alphacypermethrin applied to the dorsal mid-line of sheep with long wool and its effect on lice

A group of 5 adult Merino sheep with fleeces about 70 mm long (7-months growth of wool) was treated with a topical formulation of the synthetic pyrethroid insecticide, alphacypermethrin, applied to the dorsal mid-line. Insecticide concentrations at the tip, middle and base of wool staples collected from meridians along the back, upper and lower flanks were measured at intervals from 1 to 98 days after treatment. Some movement of the alphacypermethrin from the back to the lower body occurred within 24h after treatment, but despite careful application of the insecticide there was wide variation in the concentration between and within meridians. The majority of the alphacypermethrin remained close to the dorsal mid-line and near the tip of the staple. There were significant differences in the concentration between the tip, middle and base segments of the staples in the back and lower flank meridians (P < 0.05). Despite exposure of the sheep to normal weathering, there was no significant difference in the concentration of alphacypermethrin between samples collected at day 1 or day 98 after treatment (P > 0.05). Numbers of pyrethroid-susceptible lice surviving exposure in vitro for 20 h differed significantly between samples collected at different times after treatment (P < 0.05). The numbers of lice surviving in samples collected within 28 days after treatment tended to be lower than in those collected from 28 to 98 days but, in some samples, regardless of time after treatment, lice survived for 20 h in wool taken from parts of the fleece that contained high concentrations of alphacypermethrin.