Relationship between excision repair and the cytotoxic and mutagenic effect of the ‘anti’ 7,8-diol-9,10-epoxide of benzo[a]pyrene in human cells

The cytotoxic and mutagenic effect of (±)-7β,8α-dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti BPDE) in normally excision diploid human cells treated just prior to onset of S was compared with that of cells allowed ～ 16 h for excision repair before onset of S and with that observed in excision-deficient serodema pigmentosum (SP12BE) cells. The cells were synchronized by release from density inhibition of cell replication. DNA synthesis began ～ 22 h after the cells were plated at lower density (i.e., 1.4 × 10⁴ cells/cm²). The frequency of thioguanine-resistant mutants induced in normal cells treated just prior to onset of S was ～ 12- to 16-fold higher than that observed in cells treated in early G₁ or treated in G₀ (confluence) and then plated at lower density. The frequency approximated that expected for XP12BE cells from extrapolation of data obtained at lower doses. The frequency of mutants measured in normal cells treated in exponential growth was also much higher than that in the cells treated in early G₁ or in G₀, No such difference could be seen in XP12BE cells treated in exponential growth or in G₀. In contrast to the mutagenicity data in the normal cells, there was no significant difference in the slope of the survival curve of normal cells treated at various times prior to S phase at low densities. However, normal cells treated even at the onset of S exhibited survival equal to XP12BE cells give a 4- to 5-fold lower dose. The data support the hypothesis that DNA synthesis is the cellular event which converts unexcised DNA lesions into mutations. However, they indicate that S is not the event primarily responsible for translating DNA damage into cell death. Accompanying studies on the rate of excision of anti BPDE adducts from the normal cells during the period priot to S support the conclusions.     

A gustatory mutant of Drosophila defective in pyranose receptors

Summary Mutations in an X-linked gene, gust-A, block the responses of Drosophila melanogaster to a group of pyranose sugars. It is shown that the behavioural effects of this mutation are correlated with a loss of electrical responses in taste receptors. The mutation affects the chemoacceptors for pyranose sugars leaving the furanose acceptors intact.     

Isolation of SPO12–1 and SPO13–1 from a Natural Variant of Yeast That Undergoes a Single Meiotic Division

ATCC4117 is a strain of S. cerevisiae that undergoes a single nuclear division during sporulation to produce asci containing two diploid ascospores (Grewal and Miller 1972). All clones derived from these spores are sporulation-capable and, like the parental strain, form two-spored asci. In this paper, we describe the genetic analysis of ATCC4117. In tetraploid hybrids of vegetative cells of the ATCC4117 diploid and a/a or α/α diploids, the production of two-spored asci is recessive. From these tetraploids, we have isolated two recessive alleles, designated spo12–1 and spo13–1, each of which alone results in the production of asci with two diploid or near-diploid spores. These alleles are unlinked and segregate as single nuclear genes. spo12–1 is approximately 22 cM from its centromere; spo13–1 has been localized to within 1 cM of arg4 on chromosome VIII. This analysis also revealed that ATCC4117 carries a diploidization gene allelic to or closely linked to HO, modifiers that reduce the number of haploid spores per ascus and alleles affecting the total level of sporulation.     

Euphorigenic drugs: effects on the reward pathways of the brain.

This report summarizes a number of experiments designed to examine the changes in the threshold for intracranial self-stimulation (ICSS) in the rat after the administration of morphine and a number of narcotic agonist-antagonists, as well as three nonnarcotic drugs that have extensive nonmedical use (cocaine, d-amphetamine, and phencyclidine). The results of these experiments clearly indicate that morphine lowers the threshold for ICSS and, furthermore, there appears to be little or no tolerance to this effect. The only mixed agonist-antagonist that consistently lowered the ICSS threshold was pentazocine. Cocaine, d-amphetamine, and to a lesser degree, phencyclidine also lowered the ICSS threshold. These results suggest that the abuse liability of these agents may be directly related to their ability to sensitize the neural substrate involved with natural reward.     

Effect of ethyl acetate on the transport of sodium and glucose in the hamster small intestine in vitro.

The effect of ethyl acetate on Na+, water and glucose transport, as well as on glucose and electrolyte intracellular concentrations in everted and cannulated sacs of hamster jejunum, have been studied.Ethyl acetate, a substance that easily penetrates and delivers energy to the cell, strongly stimulates net glucose and Na+ transport. The explanation of the experimental results takes into account the possibility of the existence of an active extrusion of glucose at the level of the basolateral membrane of the enterocyte.     

Effect on ethyl acetate on the transport of sodium and glucose in the hamster small intestine in vitro

The effect of ethyl acetate on Na⁺, water and glucose transport, as well as on glucose and electrolyte intracellular concentrations in everted and cannulated sacs of hamster jejunum, have been studied.Ethyl acetate, a substance that easily penetrates and delivers energy to the cell, strongly stimulates net glucose and Na⁺ transport.The explanation of the experimental results takes into account the possibility of the existence of an active extrusion of glucose at the level of the basolateral membrane of the enterocyte.     

Synthesis and some reactions of methyl 4,6-O-benzylidene-2,3-dideoxy-2-phenylazo-β-d-erythro-hex-2-enopyranoside

Methyl 4,6-O-benzylidene-2,3-dideoxy-2-phenylazo-β-d-erythro-hex-2-enopyranoside has been synthesised, and its addition reactions with methoxide, azide, hydride, and deuteride ions have been studied. Comment is made on the stereochemistry of addition reactions of 2- and 3-phenylazo derivatives of methyl 4,6-O-benzylidene-2,3-dideoxy-d-hex-2-enopyranosides.     

Inhibition of adenylate cyclase by transglutaminase-catalyzed reactions in pigeon erythrocyte ghosts

We report the occurrence in pigeon erythrocytes of a soluble Ca2+-dependent transglutaminase (TGase) activity. The effect of the erythrocyte ghost protein modifications, determined by TGase-catalyzed reactions, on adenylate cyclase, phospholipid methyltransferase I and II activities and on the lipidic matrix fluidity of the membrane was investigated by using a purified guinea pig liver TGase preparation. The results showed a significant inhibitory effect of such modifications both on the basal and on the variously stimulated (by NaF, Gpp(NH)p alone or in the presence of 1-isoproterenol) adenylate cyclase activity. By contrast, both the phospholipid methylation and the fluidity of the lipidic matrix of the membrane were unaffected by TGase-mediated reactions. These data suggest a new possible inhibitory mechanism of the cyclic AMP synthesis which might be triggered by the enhancement of the cytosolic Ca2+ concentration.     

The genetics of complex diseases

Genetic factors influence virtually every human disorder, determining disease susceptibility or resistance and interactions with environmental factors. Our recent successes in the genetic mapping and identification of the molecular basis of mendelian traits have been remarkable. Now, attention is rapidly shifting to more-complex, and more-prevalent, genetic disorders and traits that involve multiple genes and environmental effects, such as cardiovascular disease, diabetes, rheumatoid arthritis and schizophrenia. Rather than being due to specific and relatively rare mutations, complex diseases and traits result principally from genetic variation that is relatively common in the general population. Unfortunately, despite extensive efforts by many groups, only a few genetic regions and genes involved in complex diseases have been identified. Completion of the human genome sequence will be a seminal accomplishment, but it will not provide an immediate solution to the genetics of complex traits.