Optically active benzo[c]phenanthrene diol epoxides bind extensively to adenine in DNA

Reactions of diol epoxide metabolites of carcinogenic polycyclic aromatic hydrocarbons with DNA are thought to initiate the carcinogenic process. Although formation of a benzo[a]pyrene (BaP) diol epoxide-deoxyguanosine adduct has been held responsible for biological activity, the more potent carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA) binds extensively to deoxyadenosine residues in DNA, suggesting that hydrocarbon carcinogen-deoxyadenosine adducts may be instrumental in tumour initiation. Because the bay region diol epoxides of benzo[c]phenanthrene (BcPh) are very active tumour initiators, and the relative activities of the four configurationally isomeric 3,4-diol 1,2-epoxides (Fig. 1) are known, we examined their reactions with DNA. Each BcPh diol epoxide isomer exhibits a remarkable preference for covalent binding to DNA over hydrolysis, each yields a unique distribution of products with the nucleosides of DNA and each reacts extensively with deoxyadenosine residues in DNA. The relative tumour initiating activities of these stereoisomers is best reflected by the relative yields of one of the deoxyadenosine adducts formed.     

The need for national HIV databases

Researchers and public health officials involved in surveying and forecasting the course of the HIV epidemic require complete and unfiltered information from many sources. Governments should respond by establishing national HIV databases.     

Retrograde transport by the microtubule-associated protein MAP 1C

Microtubules are involved in several forms of intracellular motility, including mitosis and organelle movement. Fast axonal transport is a highly ordered form of organelle motility that operates in both the anterograde (outwards from the cell body) and retrograde (from the periphery towards the cell body) direction. Similar microtubule-associated movement is observed in non-neuronal cells, and might be involved in secretion, endocytosis and the positioning of organelles within the cell. Kinesin is a mechanochemical protein that produces force along microtubules in an anterograde direction. We recently found that the brain microtubule-associated protein MAP 1C (ref. 7) is a microtubule-activated ATPase and, like kinesin, can translocate microtubules in an in vitro assay for microtubule-associated motility. MAP 1C seemed to be related to the ciliary and flagellar ATPase, dynein, which is thought to produce force in a direction opposite to that observed for kinesin. Here we report that MAP 1C, in fact, acts in a direction opposite to kinesin, and has the properties of a retrograde translocator.     

Absence of cooperative haemoglobin-oxygen binding in Sphenodon, a reptilian relict from the Triassic

It is generally accepted that the sigmoidal nature of the haemoglobin-oxygen dissociation curve (ODC) is necessary for efficient oxygen transport in terrestrial vertebrates because it allows large volumes of oxygen to be bound or released for relatively small changes in the partial pressure of oxygen (PO2) in the blood. Furthermore, the amount of oxygen to tissues is increased by hydrogen ions produced from the dissociation of carbon dioxide in solution. The generality of these key features of cooperative oxygen binding and the Bohr effect holds for reptiles, birds and mammals, including representatives with special respiratory requirements for diving, burrowing and living at high altitude. Sphenodon punctatus is the sole surviving representative of the ancient order of 'beakhead' reptiles (order Rhynchocephalia) which were once widely distributed during the Triassic period before the spectacular radiation of dinosaur faunas. We have now investigated the oxygen transporting properties of blood from Sphenodon and find that the ODC is hyperbolic, with a high affinity for oxygen and very small Bohr effect. This combination of characteristics is unique among terrestrial vertebrates and accords with a low demand for oxygen and limited scope for aerobic activity.     

The Tetrahymena ribozyme acts like an RNA restriction endonuclease

A shortened form of the Tetrahymena self-splicing ribosomal RNA intervening sequence acts as an endoribonuclease, catalysing the cleavage of large RNA molecules by a mechanism involving guanosine transfer. The sequence specificity approaches that of the DNA restriction endonucleases. Site-specific mutagenesis of the enzyme active site alters the substrate sequence specificity in a predictable manner, so that endoribonucleases can be synthesized to cut at a variety of tetranucleotide sequences.     

Loss of a Harvey ras allele in sporadic Wilms' tumour

Genomic changes within chromosome band 11p13 appear to have a role in the initiation of Wilms' tumour. The human Harvey ras oncogene, c-Ha-ras 1, has been located by Jhanwar et al. immediately adjacent to this region at band 11p14 .1, although several groups have assigned the gene more distally at band 11p15 . We have examined tumour DNA from two cases of sporadic Wilms' tumour, and report here that in both cases one of the two constitutional c-Ha-ras 1 alleles was absent. One tumour had a reciprocal translocation between the short arm of chromosome 11 (at band 11p13), and the long arm of chromosome 12, with no visible loss of chromosomal material. The loss of a c-Ha-ras 1 allele in association with this translocation indicates that a submicroscopic deletion had occurred. The resulting hemizygosity may have had a role in tumour initiation. Our results indicate that the c-Ha-ras 1 gene and the 'Wilms' tumour locus' may be in close proximity. It would, therefore, be premature to exclude the possibility that these two sites are functionally related.     

Tests of the helix dipole model for stabilization of alpha-helices

Charged groups play a critical role in the stability of the helix formed by the isolated C-peptide (residues 1-13 of ribonuclease A) in aqueous solution. One charged-group effect may arise from interactions between charged residues at either end of the helix and the helix dipole. We report here that studies of C-peptide analogues support the helix dipole model, and provide further evidence for the importance of electrostatic interactions not included in the Zimm-Bragg model for alpha-helix formation.     

Effect of 5-hydroxytryptamine antibodies on pigment migration in the erythrophores of the fiddler crab,Uca pugilator: Further evidence for 5-hydroxytryptamine as a neurotransmitter that stimulates release of red pigment-dispersing hormone

Summary 5-Hydroxytryptamine (5-HT) antibodies inhibit red pigment dispersion in the fiddler crab,Uca pugilator. This observation supports the hypothesis that 5-HT stimulates release of red pigment-dispersing hormone.The 5-HT antibody preparation was a generous gift from Dr S. Spector, Roche Institute of Molecular Biology, Nutley, New Jersey.     

Stereoselectivity in mammalian chemical communication: Male mouse pheromones

Two male mouse pheromones, 3,4-dehydro-exo-brevicomin (DHB) and 2-sec-butyldihydrothiazole (SBT), are chiral molecules which were previously tested in their respective bioasays as racemic mixtures. The focus of this study has been to determine the absolute configuration of their natural forms and its relation to stereospecific biological action. DHB was established as the R,R-enantiomer possessing biological activity. Due to an extremely easy racemization of SBT under very mild conditions, enantioselectivity of its transmission and its action at the receptor site appear to be of secondary importance.