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M L Aitio

Publications and source records attributed to M L Aitio.

11 recordsLinked to original sources
PubMed1992

Drug metabolism in rats with cancer induced by N-nitrosodiethylamine and phenobarbital.

The metabolism of R- and S-warfarin in vivo and in vitro, bufuralol in vitro, and antipyrine and debrisoquine in vivo were studied in rats with cancer induced by N-nitrosodiethylamine and phenobarbital treatment. Microsomal cytochrome P-450 content was greatly reduced in both healthy and cancerous parts of the livers of tumour-bearing animals. The specific activities of R-warfarin and bufuralol 1'-hydroxylases were significantly elevated in rats with cancer. The activities of S-warfarin hydroxylases expressed per mg microsomal protein were reduced in animals with cancer, whereas those of R-warfarin and bufuralol 1'-hydroxylases were not. The urinary excretion of R-7-hydroxywarfarin was increased and those of S-6- and S-4'-hydroxywarfarin decreased in rats with cancer. The correlations between microsomal formation and urinary excretion of all warfarin metabolites were poor, except for R-7-hydroxywarfarin. Antipyrine oxidation was increased in the cancerous state but the urinary metabolic profiles were similar in rats with cancer and in controls. The metabolism of debrisoquine was decreased in tumour-bearing animals. Antipyrine metabolism did not show any correlation with either warfarin or debrisoquine metabolism, whereas several relationships were observed between warfarin and debrisoquine metabolism and between warfarin and bufuralol metabolism.

Animals↗
PubMed1991

Cytochrome P-450 isozyme pattern is related to individual susceptibility to diethylnitrosamine-induced liver cancer in rats.

Differences in susceptibility to chemical carcinogenesis between rodent strains and species have been linked to variations in genetically-determined mixed function oxidase activities. In order to verify whether such variations also determine the susceptibility of individual animals of the same strain to a chemical carcinogen, outbred male Wistar rats were administered diethylnitrosamine (DEN) (1, 2, or 3 mg/kg) five times a week for 20 weeks. The relationship was examined between the outcome (i.e., presence or absence of liver tumors, and latency period) and the hepatic activities of mixed function oxidases and conjugating enzymes, as well as of O6-methylguanine-DNA-methyltransferase, measured before the carcinogen treatment. In addition, the metabolic profiles of two model drugs, antipyrine and disopyramide, in the urine were analyzed and correlated with the carcinogen susceptibility. The length of the latency period of hepatocellular tumors in individual rats was negatively related to the activities of hepatic dimethylnitrosamine N-demethylase, aryl hydrocarbon hydroxylase and epoxide hydrolase and positively related to the amount of microsomal protein. Consistent relationships between the other 10 measured parameters and the susceptibility to DEN-induced carcinogenesis were not detected. Long-term treatment with DEN slightly decreased the proportion of metabolism of antipyrine into norantipyrine, and increased the share of 4-hydroxyantipyrine; a decrease in the metabolism of disopyramide to N-deisopropyldisopyramide was also detected. It is concluded that the pattern of cytochrome P-450 isoenzymes is related to differences in individual susceptibility to nitrosamine-induced carcinogenesis. The relationship was most marked at low dose levels, which are the levels at which nitrosamine exposures of humans are known to occur.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1988

Evaluation of sister chromatid exchange as an indicator of sensitivity to N-ethyl-N-nitrosourea-induced carcinogenesis in rats.

Sister chromatid exchange (SCE) frequencies in peripheral lymphocytes are a frequently used endpoint to indicate exposures to genotoxins in groups of humans. The aim of this study was to ascertain, in an experimental design, whether or not SCE rates have any association with the risk of cancer at the individual level in rats exposed to a known carcinogen. Individual SCE rates were determined in three consecutive analyses in cultured blood lymphocytes of 50 adult male Wistar rats. Analyses were done before as well as 24 hr and 7 days after a single intraperitoneal administration of 0, 25, 50, or 75 mg/kg of N-ethyl-N-nitrosourea (ENU). The animals were followed until death; also, the relationship between SCEs and carcinogenic outcome, i.e., the presence or absence of tumors, and their latency period were examined. ENU significantly decreased the life expectancy of the rats. The tumor types most clearly associated with ENU treatment were various gliomas and thyroid-gland and testicular tumors. ENU induced a moderate (maximally 1.6-fold) increase in the mean frequency of SCEs/cell at both sampling times after treatment. The effect was somewhat more pronounced 1 day rather than 1 week after treatment. The mean SCE rates in rats with ENU-specific cancers or in animals with early or multiple tumors did not differ from those in animals that survived no less than 65 weeks or longer without developing tumors. In ENU-treated animals with tumors, no relationship was found between the mean SCE rate and survival time. It is concluded that in outbred Wistar rats the SCE response in cultured lymphocytes does not indicate individual susceptibility to the carcinogenic action of ENU. On a group basis, however, animals with high SCE rates were shown to have increased risk of cancer.

Animals↗
PubMed1979

Disopyramide.

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Disopyramide↗
PubMed1979

Induction of disopyramide N-dealkylation by phenobarbital and disopyramide in rat liver.

An in vitro assay for the determination of the activity of disopyramide-N-dealkylation was developed. This reaction was concluded to be catalyzed by the liver microsomal, cytochrome P-450 centered monooxygenase system. Phenobarbital enhanced the N-dealkylation of disopyramide four fold, and disopyramide itself 1.6 fold, whereas methylcholanthrene was without effect. Disopyramide also increased ethoxycoumarin deethylation 1.6 fold, and had a slight increasing effect on the activity of epoxide hydratase, but did not affect the activities of glutathione S-transferase or UDPglucuronosyltransferase.

Animals↗
PubMed1979

Characterization of the carcinoembryonic antigen activity associated with cyst fluids of mucinous ovarian cystadenocarcinoma.

Cyst fluids from mucinous cystadenocarcinoma of the ovary show significant concentrations of carcinoembryonic antigen (CEA) activity. This CEA activity was compared to several colon CEA standards with respect to size, concanavalin A binding, and immunological activity. CEA activity in unfractionated ovarian cyst fluid was indistinguishable from CEA standards by gel filtration chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The cyst fluid CEA activity showed identity with various CEA standards by double immunodiffusion in agar gels and by radioimmune competition assay. Attempts to purify the cyst fluid CEA by perchloric acid extraction prior to gel filtration chromatography were unsuccessful. The yield of soluble CEA activity following perchloric acid extraction averaged 10%, and in one cyst fluid, qualitative changes were noted in the soluble antigenic activity. Ovarian cyst fluid CEA activity was bound by concanavalin A-Sepharose 4B and specifically eluted with competing monosaccharide. Lectin affinity chromatography and gel filtration chromatography over Sepharose 4B and Sephadex G-200 can be used to purify cyst fluid CEA from whole fluid or lyophilized and reconstituted samples.

Carcinoembryonic Antigen↗