Hiromu Matsumoto

Studies on Methylazoxymethanol Methylation of Nucleic Acids in the Fetal Rat Brain

Summary Methylazoxymethanol, the aglycone of cycasin, reacted with nucleic acids and proteins in the fetus of rats injected with the compound on Day 14 of pregnancy. Guanine methylated in the seven position was found in both DNA and RNA. The protein reaction products were not identified. The distribution of the injected compound in the tissues and fluids of the mother rat was determined. This communication is published as Hawaii Agricultural Experiment Station Journal Series No. 1111. This investigation was supported in part by Public Health Service Research Grant NB-3909 from the National Institute of Neurological Diseases and Blindness, U. S. Public Health Service.

QUANTITATIVE CHANGES WITH AGE IN THE DNA CONTENT OF METHYLAZOXYMETHANOL-INDUCED MICROENCEPHALIC RAT BRAIN

Abstract— DNA synthesis in methylazoxymethanol (MAM)‐treated foetal brain was reduced during the first 3 days after the injection of the compound into the mother rat. The MAM‐treated brain grew at almost the normal rate after this period, but the reduction in DNA persisted through maturity of the animal. This difference in DNA content between normal and microencephalic brain was restricted to the cerebral hemispheres. The major increase in DNA content of prenatal brain occurred in the cerebrum, whereas the postnatal increase took place in the cerebellum. jH‐Labelled MAM was incorporated more extensively into foetal brain DNA than into RNA. The half‐life of the MAM‐modified nucleic acids was 4–5 days. We suggest that removal of necrotic cells from the brain may account for the rapid loss of label from nucleic acids.

STUDIES ON METHYLAZOXYMETHANOL, THE AGLYCONE OF CYCASIN. ISOLATION, BIOLOGICAL, AND CHEMICAL PROPERTIES.

Abstract The glucoside cycasin administered intraperitoneally to rats is almost quantitatively excreted unchanged in the urine with no apparent toxicity. Oral administration results in severe toxicity and greatly reduced urinary excretion of cycasin. Methylazoxymethanol (MAM), the aglycone of cycasin prepared by enzymic hydrolysis of cycasin proved to be toxic when injected. Thus it was demonstrated that the toxic component is the aglycone and not cycasin per se. Experimental details for the preparation of MAM by enzymic hydrolysis of cycasin and the properties of three derivatives of MAM are described.

A rapid colorimetric method for the determination of mimosine

Abstract A rapid colorimetric method has been described for the quantitative determination of mimosine by using activated carbon as a decolorizing agent and measuring the intensity of mimosine-ferric chloride color produced.

The biosynthesis of 3-nitropropanoic acid by Penicillium atrovenetum.

Maximum production of 3-nitropropanoic acid by Penicillium atrovenetum occurs when the culture medium contains an auxiliary carbon source and ammonium ion. The most suitable carbon sources are dicarboxylic acids such as fumaric, succinic, and tartaric. Aspartic acid is presumably deaminated prior to its utilization in the biosynthesis. The addition of an oxidized form of ammonia to fumarate is proposed as a possible first step in the biosynthetic sequence.

The Effect of elevated temperatures on the mimosine content and toxicity of koa haole (Leucaena glauca)

Abstract When koa haole leaves were stored at elevated temperatures the mimosine content was decreased. The effect was most pronounced and rapid when the temperature was over 70 °C. in the presence of moisture. A similar effect occurred in seeds when sufficient moisture was present. The phenomenon did not take place in dry leaves. Steam was effective in extracting mimosine from koa haole leaves. Heated koa haole leaf meal has been demonstrated to be less toxic than unheated koa haole leaf meal when the meals are fed to albino rats as part of their rations. The development of alopecia in rats fed unheated koa haole meal has been described, and the growth curves of rats fed heated and unheated leaf meals and basal rations have been compared. Ferrous sulfate added to rations containing unheated koa haole leaf meal has been shown to be effective in reducing mimosine toxicity.

Research progress on cycads

The multiple facets of cyead research are apparent by sponsorship of a conference by three of the National Institutes of Health: National Institute of Neurological Diseases and Blindness (NINDB), National Institute of Arthritis and Metabolic Diseases (NIAMD), and National Cancer Institute (NCI). Approximately 50 persons attended the oneday meeting held at Bethesda, Maryland, to discuss the progress which has been made within the past year.3 The family Cycadaceae are palm-like plants which have survived from the Mesozoic era with little evolutionary change. There are nine living genera distributed in tropical and subtropical areas of the world. In areas where the cycad is indigenous, the starchy portion (seed, rhizome or stem) provides a source of food and laundry starch. Sprouts and leaves are used as green vegetables and dried husks of the seed provide a tasty chew. Fresh sap promotes healing of open wounds. New sprouts and young leaves are consumed by grazing animals, especially in early spring or following drought or burning when the cyead may be the only green plant available. Although native populations recognize the toxicity of the cycad when it is used as food and follow prescribed precautions in its preparation, several cases are recorded in which acute toxic effects have followed consumption of inadequately prepared starch. The genera, Macrozamia, Cycas, Zamia, and Encephalartos, have been implicated in toxic effects on human beings. Although the significant advances by

Methemoglobinemia in rats injected with 3-nitropropanoic acid, sodium nitrite, and nitroethane☆

Injection of sodium nitrite, 3-NPA, or nitroethane into rats produced methemoglobinemia in the order of decreasing effectiveness. The methemoglobin level reached 50% after administration of sodium nitrite, but the animals survived whereas animals having a methemoglobin level higher than 25% after injection of 3-NPA died. Nitroethane proved nontoxic at the concentrations used. Incubation in vitro of 3-NPA, and nitroethane with blood, did not produce methemoglobin. Excretion is not a major mode of detoxication. It is proposed that 3-NPA is degraded in vivo, at a site other than the circulatory system, with the production of nitrite and an unidentified carbon compound.

INHIBITION OF SUCCINIC DEHYDROGENASE BY 3-NITROPROPANOATE.

Abstract 3-Nitropropanoate (3-NPA) has been shown to be a competitive inhibitor of rat heart muscle succinic dehydrogenase. The dissociation constant Ki 3-NPA has been determined to be 184–200× 10 −4 . 3-NPA is approximately one-twentieth as powerful an inhibitor of this enzyme as malonate.