ABSTRACT. Activities of malate dehydrogenase (MDH) and aspartate aminotransferase in the malate-aspartate shuttle were significantly increased in the cytosolic fractions of livers with early neoplastic symptoms such as swelling and discoloration in transgenic mice carrying the prototype human c-Ha-ras gene, Tg-rasH2 mice, which were administered with diethylnitrosamine (DEN) as a carcinogenic chemical at a dose of 200 mg/kg body weight. Cytosolic MDH/LDH (lactate dehydrogenase) (ML) ratio increased significantly and w as considered to be a useful marker to characterize the energy metabolism at early neoplastic stage in livers of the Tg-rasH2 mice. KEY WORDS: aspartate aminotransferase, malate dehydrogenase, transgenic mouse.J. Vet. Med. Sci. 64(11): 1065-1067, 2002 A transgenic mouse strain carrying human prototype cHa ras gene, Tg-rasH2 mice, was established by Saitoh et al. [20]. These mice show high and rapid susceptibility to various carcinogens and are considered to be promising as an animal model for an alternative rapid carcinogenicity test [25]. Spontaneous hepatocellular carcinomas, forestomach papillomas, skin papillomas and lymphomas were observed in 20 to 30% of Tg-rasH2 mice by 82 weeks and these incidences were increased by treatments of some kinds of carcinogens including N,N'-diethylnitrosamine (DEN) known as Salmonella mutagenesis assay-positive trans-species carcinogen [24]. The major target organs of DEN are the liver, lung, forestomach and hematopoietic system [12]. In our previous reports, Tg-rasH2 mice were characterized by stable activities of some enzymes related to drug detoxication and energy metabolism in their livers and kidneys compared to those in the non-transgenic control [18]. On the other hand, it has been reported that activities of enzymes in the glycolysis and the pentose phosphate pathway are significantly increased in developed tumor cells [1,7,17]. Activities and mRNA expression of malate dehydrogenase (MDH) in the malate-aspartate shuttle are significantly induced in the early stage of testicular tumor of dogs [3]. In the present study, activities of several enzymes related to energy metabolism were measured in livers of the Tg-rasH2 mice treated with DEN to investigate availability of certain enzymes as a diagnostic marker for energy metabolism at the early stage in tumor cells.F1 hybrids of a transgenic male C57BL/6J, Tg-rasH2, mice and normal female BALB/cByJ mice were used. The F1 offsprings were screened by polymerase chain reaction (PCR), and divided into transgenic (-/Tg) and non-transgenic mice (-/-). Six-week-old male transgenic mice, which showed high expression of ras gene, were used in the present study. Their mean (± SD) body weights were 16.8 (± 0.4) g. Mice were housed in an air-conditioned room (23 ± 2°C, 55 ± 10%) with a light period of 12 hr. Food and water were available ad libitum. All procedures involving laboratory animals were performed in accordance with the care and use guidelines of the Central Institute of Experimental Animals (Kawasaki, Japan)...
Changes in the activities of enzymes related to energy metabolism in the testicular tissues of dogs with seminoma were investigated. The testis was removed surgically from animals anaesthetized with halothane. Cytosolic and mitochondrial fractions were isolated and the total RNA was extracted from testicular homogenates. The activities of enzymes related to energy metabolism were measured and the mRNA of cytosolic malate dehydrogenase (MDH) was investigated by the reverse transcriptase-polymerase chain reaction (RT-PCR). The activities of the glycolytic enzymes glucose-6-phosphate dehydrogenase (G6PD) for the pentose phosphate pathway and malate dehydrogenase (MDH) for the malate-aspartate shuttle, and the expression of the mRNA of cytosolic MDH were significantly increased in the testicular tissues of dogs with seminoma. These enzymatic activities may be useful indicators with which to evaluate changes in the metabolic conditions in testicular tissues of dogs with seminoma.
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