Induction of congenital anomalies in offspring of female mice exposed to varying doses of X-rays

Female mice were exposed to varying absorbed doses (108–504 rad) of X-rays and mated at different intervals after irradiation (1–7, 8–14, 15–21 and 22–28 days). Uterine contents were examined at late pregnancy in order to detect early fetal deaths (dominant lethality) and malformations in the live fetuses.Two trends were apparent from data on abnormal fetuses. At each weekly interval, the incidence of abnormalities tended to rise with increase in dose, and, at any given dose, the incidence tended to increase with time after irradiation. Dwarfism and exencephaly were the two most common malformations found.The changes in incidence of dominant lethality and of abnormal fetuses with time and with dose follow each other closely, the highest incidence for both being reached in week 3 (59±4.7% for dominant lethals and 12.5±3.1% for abnormal fetuses, after 504 rad) indicating increased radiosensitivity of less mature oocytes. These results parallel those obtained from known genetic effects reported by other workers and suggest that testing for incidence of congenital malformations among offspring of treated animals may prove a useful means of assessing genetic hazards of radiation of chemicals.     

Combination v. sequential therapy with melphalan, 5-fluorouracil and methotrexate for advanced ovarian cancer.

The results of a national clinical trial to compare combination and sequential chemotherapy for stage III or IV ovarian cancer are reported. Of the 253 patients from 16 centres across Canada who were admitted to the trial 13 were excluded from the analysis. All the patients were observed for 2 to 5 years from entry into the trial. There were no differences in response to therapy or in survival between the patients treated with melphalan followed by 5-fluorouracil and then by methotrexate in high dosage and the patients treated with the same agents in combination. Patients with minimal residual disease after resection of stage III ovarian cancer had a good prognosis. Other favourable prognostic factors were age (less than 55 years), performance status (90% or 100% on the Karnofsky scale) and histologic grade of the tumour.     

The life history and host specificity of theEchium borer,Phytoecia coerulescens [Col.: Cerambycidae]

The cerambycid stem borerPhytoecia coerulescens (Scopoli) is a possible biological control agent for the weedEchium plantagineum L. in Australia. The adult beetle oviposits at the base of stems ofEchium spp. and a few otherBoraginaceae. The larva damages the flower stem by boring both upwards and downwards and eventually, at the end of the season, girdling the stem at its base. It overwinters in the rootstock of its host plant. It does not attack plants of agricultural importance in the field and host restriction to a small group of boraginaceous plants was confirmed in the laboratory, withEchium spp. as principal hosts. It is therefore considered thatP. coerulescens is a safe agent to introduce into Australia for the control ofE. plantagineum.     

Antimetabolic activities of 2-fluoro-L-histidine.

2-Fluoro-L-Histidine inhibits protein synthesis in various cell cultures, as measured by ³H-leucine incorporation. This histidine analog also inhibits the cytopathogenicity of a number of RNA and DNA viruses in primary and continuous cell cultures; it blocks the transformation of normal mouse (MO) cells by murine sarcoma virus, and partially suppresses the release of murine leukemia virus by a continuously infected mouse cell line (JLSV5). In human skin fibroblasts, it reduces the interferon-inducing capacity of poly(I)·poly(C). Inhibition of cell protein synthesis may be the common cause of the various effects. 4-Fluoro-L-histidine is essentially inert in all of the test systems examined.     

Comparison of fatty acid oxidation in mitochondria and peroxisomes from rat liver

Oxygen uptake with succinate or palmitoyl-CoA as substrates can be measured in rat liver mitochondria that have been isolated by sucrose density gradient centrifugation providing the fractions are diluted with a 30 mM phosphate buffer rather than with an isotonic medium. Separate assay procedures were used to measure peroxisomal and mitochondrial β-oxidation of palmitoyl-CoA in the fractions of a sucrose gradient used to separate these organelles. A preliminary estimate of the ratio of palmitoyl-CoA oxidation by the mitochondrial fraction relative to the surviving peroxisomes from livers of male rats was 3.2.     

Rates of synthesis and source of glycolate in intact chloroplasts

Summary Intact chloroplasts capable of high rates of CO₂ assimilation completely oxidized 3-phosphoglycerate and dihydroxyacetone phosphate to glycolate when CO₂ concentrations were low. Bicarbonate was converted first into products of the Calvin cycle and then into glycolate. Under high oxygen and at high pH values CO₂ fixation and glycolate formation ceased before bicarbonate was exhausted. This is interpreted as the consequence of a depletion of ribulose diphosphate (RuDP) at the oxygen compensation point, where oxygen consumption by glycolate formation and oxygen evolution by phosphoglycerate reduction balance each other. Depletion of RuDP by glycolate formation is proposed to play a role in the Warburg effect. The maximum rate of glycolate synthesis observed with dihydroxyacetone phosphate as substrate was 35 mol mg^-1 chlorophyll h^-1 at 20°C. This may not reflect the maximum capacity of chloroplasts for glycolate synthesis. Dithiothreitol and catalase, which prevent accumulation of oxygen radicals or H₂O₂ during carbon assimilation, increased glycolate formation. H₂O₂ was inhibitory. Other inhibitors of glycolate formation were glyceraldehyde and carbonylcyanide p-trifluoro-methoxphenylhydrazone. From the sensitivity of glycolate synthesis to uncoupling and the ATP requirement of RuDP formation it is concluded that glycolate originated from RuDP. Different induction periods of carbon fixation and glycolyte formation suggested that glycolate synthesis is not only regulated by the ratio of oxygen to CO₂ but also by another factor.     

Synthesis of 18-substituted steroids Part II (1). Improvements in the preparation of 18-hydroxyprogesterone.

18-Hydroxyprogesterone is conveniently prepared from 3beta-acetoxypregn-5-en-20beta-ol by a modified route. 3beta-Acetoxy-18-iodopregn-5-en-20-one, obtained by the hypoiodite-photolysis procedure and oxidation, is treated with methanolic silver acetate to give the 18, 20-epoxy-20-methoxy derivative, which crystallises directly without need for chromatography. Hydrolysis of the 3-acetate, and a modified Oppenauer oxidation, gave 18-hydroxy-progesterone in 24% over-all yield.     

Use of pattern recognition to classify beef cardiovascular tissues on the basis of their trace metal compositions.

The pattern recognition procedure of discriminant analysis has been used to characterize the trace metal profiles created by the concentrations of 8 trace metals in 15 anatomic sites of beef heart tissue. Metals analyzed were copper, tin, lead, molybdenum, strontium, cesium, barium, and aluminum. Anatomic sites sampled included main pulmonary artery, aorta, mitral and tricuspid valves, left and right coronary arteries, os cordis, right atrium, left atrial appendage, crista supraventricularis, left bundle branch, free wall of the right and left ventricles, interventricular septum, and papillary muscle of the left ventricle. The striking features of the data were: (1) All specimens of the mitral valve, tricuspid valve, and os cordis were ambiguously described by their trace metal profiles; (2) the four blood vessels constituted two groups of two tissues each (aorta, main pulmonary artery; left and right coronary arteries); (3) tissues derived from ordinary and specialized myocardium were quite different from blood vessels, heart valves and os cordis. Using these profiles, 85% of the specimens analyzed were correctly classified by discriminant analysis with respect to their anatomic origin.     

Reduction of oxygen by the electron transport chain of chloroplasts during assimilation of carbon dioxide

In photosynthetically competent chloroplasts from spinach the quantum requirements for oxygen evolution during CO₂ reduction were higher, by a factor often close to 1.5, than for oxygen evolution during reduction of phosphoglycerate. Mass spectrometer experiments performed under rate-limiting light indicated that an oxygen-reducing photoreaction was responsible for the consumption of extra quanta during carbon dioxide assimilation. Uptake of ¹⁸O₂ during reduction of CO₂ was considerably higher than could be accounted for by oxygen consumption during glycolate formation and by the Mehler reaction of broken chloroplasts which were present in the preparations of intact chloroplasts. The oxygen reducing reaction occurring during CO₂ assimilation resulted in the formation of H₂O₂. This was indicated by a large stimulation of CO₂ reduction by catalase, but not of phosphoglycerate reduction. Catalase could be replaced as a stimulant of photosynthesis by dithiothreitol or ascorbate, compounds known to react with superoxide radicals. There was no effect of dithiothreitol and ascorbate on phosphoglycerate reduction. A main effect of superoxide radicals and/or H₂O₂ was shown to be at the level of phosphoglycerate formation. Evidence for electron transport to oxygen was also obtained from ¹⁴CO₂ experiments. The oxidation of dihydroxyacetonephosphate during a dark period or after addition of carbonyl cyanide p-trifluoromethoxyphenylhydrazone in the light was studied. The results indicated a link between the chloroplast pyridine nucleotide system and oxygen. Oxygen reduction during photosynthesis under conditions where light is rate limiting is seen as important in supplying the ATP which is needed for CO₂ reduction but is not provided during electron transport to NADP. A mechanism is discussed which would permit proper distribution of electrons between CO₂ and oxygen during photosynthesis.