Sex-related Resistance in Hamsters to Adenovirus-12 Oncogenesis II. Influence of Virus Dose

A significantly higher proportion of female hamsters developed tumors than did males given the same dose of adenovirus-12 (Huie) at birth over a dose range from 10(5.0) to 10(7.0)tcd(50) for human embryonic kidney cells. The 50% tumor dose (td(50)) was calculated to be 10(5.90)tcd(50) for females and 10(6.27) for males. Tumor response patterns induced with approximate td(50) inocula, 10(6.0) for females and 10(6.3) for males, were quite similar. The greater susceptibility of females was not found to be characteristic of a single strain of hamsters; nor was it attributable to a single lot of virus, to a single type of human cell used to produce the virus, nor to the degree of purification of the virus inoculum. The inoculation route did not appear to be of importance. Inasmuch as the foregoing extrinsic factors were of little influence, it was concluded that the mechanism is host-mediated, presumably hormonally controlled. The possibility that female cells, independent of host control, are more susceptible to adenovirus-12 oncogenesis than male cells has not been explored. Tumor regression occurred in 20% of the 211 tumors in males and in 15% of the 355 tumors in females. Adenovirus-12 T-antibody was detected in all but six of 473 sera tested from tumor-bearing hamsters and in 50% of 94 sera tested from non-tumor-bearing animals given virus at birth. Antibodies in the latter group were detected almost exclusively by indirect immunofluorescence. This technique appears to be extremely sensitive for detection of low levels of adeno-12 T-antibodies. The implications of T-antibody in nontumor-bearing virus-injected hamsters are discussed. Sera from normal hamsters were free of T-antibody.     

Circular dichroism measurements of benzyl L-aspartate–nitrobenzyl L-aspartate copolymers and their use in detecting and characterizing preferred polymer conformations

We have examined the nature of the circular dichroism band at 330 mμ for a series of copolymers of β-p-nitrobenzyl L -aspartate with β-benzyl L -aspartate. The circular dichroism band arises from an electronic transition in the nitroaromatic group. In order to interpret the effect quantitatively, we employed a simplified statistical treatment and curve fitting for six copolymers. Both approaches gave consistent results, which indicates that the dichroism comes from pairwise interactions between two nitrobenzyl groups. We constructed a molecular model that meets the constraints and requirements of the analyses developed in this paper. In this model, it is proposed that the main chain forms a right-handed α-helix and that nitrobenzyl groups separated by four residues interact with each other.     

Inhibition of purine phosphoribosyltransferases from Ehrlich ascites-tumour cells by purine nucleotides

1. The purine bases adenine, hypoxanthine and guanine were rapidly incorporated into the nucleotide fraction of Ehrlich ascites-tumour cells in vivo. 2. The reaction of 5'-phosphoribosyl pyrophosphate with adenine phosphoribosyltransferase from ascites-tumour cells (K(m) 6.5-11.9mum) was competitively inhibited by AMP, ADP, ATP and GMP (K(i) 7.5, 21.9, 395 and 118mum respectively). Similarly the reactions of 5'-phosphoribosyl pyrophosphate with both hypoxanthine phosphoribosyltransferase and guanine phosphoribosyltransferase (K(m) 18.4-31 and 37.6-44.2mum respectively) were competitively inhibited by IMP (K(i) 52 and 63.5mum) and by GMP (K(i) 36.5 and 5.9mum). 3. The nucleotides tested as inhibitors did not appreciably compete with the purine bases in the phosphoribosyltransferase reactions. 4. It was postulated that the purine phosphoribosyltransferases of Ehrlich ascites-tumour cells may be effectively separated from the adenine nucleotide pool of these cells.     

Histone differentiation and nuclear activity

When fast green and eosin are used in combination to stain histones, nuclei display different affinities toward the dyes, some binding fast green exclusively, others binding eosin exclusively, and still others, both stains. In a given tissue, the frequencies of nuclei exhibiting the different colors remain fairly constant over a wide range of staining conditions. Nuclei of cells of the same type may stain differently, but when they are in the same stage of development or state of activity they tend to stain alike. Xenopus erythrocyte nuclei stain bright pink. Condensed mitotic and meiotic chromosomes stain purple. In the grasshopper spermatocyte, the main body of the interphase nucleus stains bright green, but the condensed chromosome stains purple. The mole crab sperm contains several distinct histone-like proteins, that differ in their amino acid compositions, within separate areas of the cell. In these sperms, the lysine-rich histones bind eosin, while the protamine-like protein and arginine-rich histone bind fast green. In general, the eosin and fast green bind preferentially to the lysine and arginine rich histones respectively, when the dyes are permitted to compete with one another. In several systems, including spermiogenesis and erythropoiesis, the aquisition of an eosinophilic component by the nuclei accompanies the slowing of RNA synthesis, and it is suggested that there may be a causal relationship between the two events, the eosinophilic histone effecting RNA synthesis within the nucleus as a whole.     

Some facts concerning the nature and formation of axial core structures in spermatids of Gryllus domesticus

Examination of living spermatid nuclei of Gryllus domesticus has revealed the presence of the same structures, the X chromosome, the round body and the axial core structures, which have been described from electron microscopic observations. The outer ribbons of the axial core structures and the round body are composed of 100 Å fibres indiscernible from and often continuous with the fibres composing the X chromosome. That the outer ribbons of the axial core structures and the round body are chromosomal is further substantiated by the results of cytochemical examinations of formaldehyde fixed material which show that the axial core structures and the round body contain RNA, DNA and basic protein. Neither acetic acid-ethanol nor cold ethanol fixation preserve the round body and the axial core structures suggesting that a protein may be responsible for maintenance of the central core structure. The central core structures are always found in close association with condensed chromatin in regions where the chromosome elements are about 1000 Å apart, suggesting that the relative state of condensation of the chromatin and the spacial relationship between condensed regions may be two of the chief factors concerned in central core formation. Maintainance of the condensed state of the chromatin, however, may in turn depend upon central core integrity.Herrn Prof. J. Seiler zu seinem 80. Geburtstag gewidmet.     

MITOCHONDRIA IN CARDIAC MUSCLE CELLS OF THE CANARY AND SOME OTHER BIRDS

The fine structure of mitochondria from the ventricular myocardium of canaries, sparrows, zebra finches, quail, and geese has been studied. The first three of these birds have very fast heart rates, the quail being intermediate, and the goose has a relatively slow rate. The canary heart has a unique form of mitochondrion containing large, parallel arrays of zigzag or angled cristae. Other cristae, continuous with the zigzag ones and also occupying large parts of the mitochondrial volume, are named retiform because of the hexagonal network which they form, sometimes in a single plane and sometimes three dimensional. These two types of cristae appear to be interconnectible. It is possible that there is a direct functional significance in these peculiar forms, but, in any case, the relative constancy of dimensions in these arrays is probably related to specific properties of the molecules of which the cristal membrane is composed. It is also demonstrated that this membrane is composed in part of approximately 30-A particles which are believed to be protein molecules. This unusual mitochondrial morphology is not seen either in the other fast bird hearts or in the slower ones, so that there is neither a simple correlation with heart rate nor probably with the separate parts of the cardiac cycle. Although none of the other four hearts shows more than an occasional angled crista, there does seem to be a rather gross correlation between heart rate and mitochondrial size and complexity of crista structure, but no correlation with presence or absence of zigzag forms. The cristae of quail heart mitochondria are disposed in unusually large close-packed whorls.