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.     

Formation of lipoperoxide in isolated sciatic nerve by chinoform-ferric chelate.

Effects of chinoform and chinoform-ferric chelate on formation of lipoperoxide in isolated sciatic nerve were investigated. Free chinoform did not increase the lipoperoxide level, while chinoform-ferric chelate significantly increased it. Assuming that the lipoperoxide formed denatures the associated protein in the nerve, the effect of chinoform-ferric chelate could explain, at least partly, the demyelination of nerve tissues caused by massive doses of chinoform.     

Distribution of type A and B monamine oxidase activities in the central nervous system of rat and chick.

The distribution of type A and B monamine oxidase (MAO) activities in the central nervous system (CNS) of rat and chick was investigated using 5-hydroxytryptamine and beta-phenylethylamine as specific substrates. The distribution of type A MAO was similar to that of type B MAO in rat CNS, but quite different in chick CNS. This may be ascribed to the difference in animal species. The major part of MAO activity in the spinal cord was found to be type A.     

Lipoperoxide formation in the retina in ocular siderosis

Summary Insertion of iron nail into the vitreous cavity provoked the formation of lipoperoxide in the retina. In accord with the increase in lipoperoxide in the retina, ERG began to decrease. In vitro experiment using isolated retina, lipoperoxide was found to be increased in the presence of ferric or ferrous ions, while it was inhibited by adding antioxidants or ethylenediamine tetraacetate. From these results, direct cause of retinal degeneration in siderosis could be ascribed to the formation of lipoperoxide by iron-ions liberated from the piece of iron, resulting into the degeneration of the visual cell layers of the retina.     

Formation of lipoperoxide in the retina of rabbit exposed to high concentration of oxygen.

When rabbit was exposed to high concentrations of oxygen, lipoperoxide in the retina was increased at 12 h of the exposure, after which period amplitude of electro-retinogram decreased. The degeneration was observed in the visual cell layer of the retina of the exposed animal.The exposure increased lipoperoxide in isolated retina. These data show the intervention of lipoperoxide in retinal degeneration by exposure to high concentration of oxygen.     

Interaction of chinoform with electron transfer system of rat liver microsomes

Zusammenfassung Nachweis, dass Chinoform, 5-chloro 7-iodo 8-quinolinol, mit Mikrosomen der Rattenleber weder hydroxyliert noch dehalogeniert werden kann. Inkubation mit Chinoform vermindert die Komponenten des elektronischen Transfersystems, was auch mit in vivo-Versuchen festgestellt wurde.     

Expression of the mutant gene for L-gulono-γ-lactone oxidase in scurvy-prone rats

A mutant strain of Wistar rats with L-gulono--lactone oxidase deficiency has recently been established. To investigate this deficiency by DNA and RNA blot hybridization analyses, a fragment of a previously cloned cDNA encoding rat L-gulono--lactone oxidase was used as a probe. When genomic DNA of the mutant rat was digested with several restriction enzymes, the probe hybridized to fragments of the same sizes as those produced from DNA of normal rats. Poly(A)⁺RNA from the liver of the mutant rat was found to contain an L-gulono--lactone oxidase-specific mRNA of a normal size at a comparable level to that of normal rats. An in vitro translation experiment revealed that the mRNA programmed the synthesis of an enzyme protein which had the same molecular weight as that of the translational product of the normal mRNA, although the amount synthesized was markedly reduced as compared with that synthesized with the normal mRNA. In accordance with this observation, a very low but definite degree of L-gulono--lactone oxidase activity was detected in the microsomes of the mutant rat by a newly developed, highly sensitive method.Acknowledgments. The authors thank Dr Susumu Makino, Shionogi Research Laboratories, Shionogi & Co., Ltd, Japan, for his kind donation of normal (ODS- +/+) and ODS (ODS-od/od) rats. This work was supported in part by Grant-in-Aid (59570103) for Scientific Research from the Ministry of Education, Science and Culture of Japan.     

Distribution of type A and B monoamine oxidase activities in the central nervous system of rat and chick

Summary The distribution of type A and B monoamine oxidase (MAO) activities in the central nervous system (CNS) of rat and chick was investigated using 5-hydroxytryptamine and -phenylethylamine as specific substrates. The distribution of type A MAO was similar to that of type B MAO in rat CNS, but quite different in chick CNS. This may be ascribed to the difference in animal species. The major part of MAO activity in the spinal cord was found to be type A.