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Biomedical subjects

M C Archer

Publications and source records attributed to M C Archer.

143 records · Page 8Linked to original sources
PubMed1975

Inhibitor of Clostridium perfringens formed by heating sodium nitrite in a chemically defined medium.

An inhibitor of Clostridium perfringens formed when low levels of nitrite were autoclaved with a defined chemical medium. A systematic study of the medium revealed that only amino acids and mineral salts were involved in the production of this inhibitor, which was proven to be a toxic compound formed from cysteine, ferrous sulfate, and sodium nitrite. The inhibitor was compared to several known compounds. S-nitrosocysteine inhibited the test organism, but would not form in the test system in amounts large enough to explain the observed inhibition. Roussin red salt was unstable in the test system and therefore was not the inhibitor. Roussin black salt, which was also inhibitory, could form in sufficient amounts to explain the inhibition. A complex of cysteine, iron, and nitric oxide was detected in the autoclaved solution of cysteine, ferrous sulfate, and sodium nitrite; this cysteine complex did not appear to be inhibitory, however, at levels which could form in the autoclaved medium. The observed inhibition may have been due to the combined effects of sublethal concentrations of each compound.

Anti-Bacterial Agents↗
PubMed1975

Carcinogenicity of nitrosation products of ephedrine, sarcosine, folic acid, and creatinine.

Carcinogenic activity of several synthetic N-nitroso compounds was evaluated in C57BL/6J X C3HeB/FeJ F1 mice. Test substances, suspended in trioctanoin, were injected i.p. in three equal doses given on Days 1, 4, and 7 after birth and animals were held without further treatment for up to 85 weeks. Nitrosoephedrine at a total dose of 600 mg/kg induced metastasizing liver cell carcinomas in 28 of 30 animals. Nitrososarcosine (225 mg/kg) induced similar tumors in 8 of 14 animals. Nitrosofolic acid (375 mg/kg) induced lung adenocarcinomas in 4 of 28 mice. Creatinine-5-oxime (600 mg/kg) showed no evidence of carcinogenic activity. Diethylnitrosamine (12 mg/kg given in four doses), included as a positive control, caused metastasizing liver cell tumors in 23 of 25 animals.

Adenoma, Bile Duct↗
PubMed1974

Formation of N-nitrosopyrrolidine in a dog's stomach.

The formation of N-nitrosopyrrolidine from sodium nitrite and pyrrolidine in vivo in a dog's stomach is demonstrated. The rate of formation of nitrosopyrrolidine is shown to be subject to pronounced catalytic effects. Nitrosopyrrolidine is also shown to disappear rapidly from the stomach, probably due to absorption.

Animals↗
PubMed1971

Environmental nitroso compounds: reaction of nitrite with creatine and creatinine.

Creatine reacts with nitrite under acid conditions to produce first sarcosine and then N-nitrososarcosine, which is a weak carcinogen in the rat. Creatinine reacts with acidified nitrite to produce either creatinine-5-oxime or 1-methylhydantoin-5-oxime, depending on reaction conditions. The toxicity and environmental significance of these compounds is not yet known.

Carcinogens↗
PubMedDate not supplied

Base-catalyzed decomposition of N-nitrosobis(2-oxopropyl)amine.

N-Nitrosobis(2-oxopropyl)amine, a potent carcinogen for the pancreas in Syrian hamsters, undergoes a facile, base-catalyzed, intramolecular aldol condensation to yield N-nitroso-5-hydroxy-5-methyl-3-piperidone. This cyclic nitrosamine then decomposes to yield 3-hydroxy-5-methylpyridine.

Carcinogens↗
PubMedDate not supplied

Evidence that the hepatotoxicity of N-nitrosodimethylamine in the rat is unrelated to DNA methylation.

N-Nitrosodimethylamine (NDMA) is a potent hepatotoxicant in the rat, but the mechanism by which it lethally injures hepatocytes is not known. NDMA is metabolized in the liver to the methanediazonium ion that methylates hepatic DNA. Neither N-nitrosomethylbenzylamine (NMBzA) nor methylnitrosourea (MNU) produces liver tumors, but via metabolism in the case of NMBzA, or via spontaneous decomposition at physiological pH in the case of MNU, both compounds produce the methanediazonium ion and methylate hepatic DNA. Here we have compared quantitatively the ability of NDMA, NMBzA, and MNU to cause lethal injury to hepatocytes in vivo and to produce O6-methylguanine in hepatic DNA. Neither NMBzA nor MNU produced hepatotoxicity in the rat even at doses as high as 667 mumol/kg body wt for NMBzA and 971 mumol/kg body wt for MNU. NMBzA given at the same time as NDMA potentiated the hepatotoxicity of NDMA, but O6-methylguanine levels were only additive. MNU did not potentiate the hepatotoxicity of NDMA, but again, the O6-methylguanine levels were additive when NDMA and MNU were administered together. These results appear to rule out the involvement of DNA methylation in lethal hepatocyte injury by NDMA.

Animals↗
PubMedDate not supplied

Zonal location of compensatory hepatocyte proliferation following chemically induced hepatotoxicity in rats and humans.

Hepatocyte proliferation stimulated by partial hepatectomy occurs first in periportal cells, with midlobular and then perivenous cell division occurring later. We have previously shown that this pattern of compensatory cell proliferation also occurs following the hepatotoxicity of N-nitrosodimethylamine. We examined the generality of this pattern in livers of rats given a minimally toxic dose of an hepatotoxin and in liver biopsy samples from patients who had taken overdoses of acetaminophen. Proliferating hepatocytes were detected immunohistochemically (5'-bromodeoxyuridine or Ki-67 antigens). The perivenous necrogens N-nitrosodiethylamine, carbon tetrachloride (CCl4), bromobenzene, and acetaminophen all induced periportal hepatocyte proliferation. With CCl4, bromobenzene, and acetaminophen, the initial appearance of proliferating periportal hepatocytes was followed 12-24 hr later by division in the midlobular region, with a few cells dividing adjacent to the perivenous region of necrosis. The periportal necrogen allyl alcohol also induced periportal cell division. In the human studies, perivenous necrosis was accompanied by periportal and midlobular hepatocyte proliferation. These results suggest that regardless of its lobular location chemically induced hepatotoxicity stimulates cell proliferation that begins in the periportal zone and then moves in an orchestrated response into the midlobular and perivenous zones.

Acetaminophen↗