The effect of psychoemotional state on Lewis lung carcinoma metastasis

The effect of a depression-like status formed by chronic stress on development of Lewis lung carcinoma metastases in C57Bl/6J mice was investigated. Two types of acute stress (restraint and social stress) were used for comparison. The depression-like status was induced by eight-week exposure to repeated but unpredictable stressors (chronic mild stress model) and was assessed in the forced swim test. Tumor cells were inoculated an hour after the onset of social stressor or immediately after physical or chronic stressor impacts. The number of metastases was counted 17 days after the inoculation. The results indicate that chronic mild stress provokes the development of a depression-like state in mice and causes a twofold increase in the number of metastases in the lungs, while both types of acute stress have no such effects. Thus, a depression-like psychoemotional status of animals enhances the metastasis of Lewis lung carcinoma.     

The study of correlation between the K-ras genotype and murine susceptibility to chemically induced lung neoplasms

The susceptibility of the ICR, DD/He and CC57/BR mice to urethane-induced lung tumors was analyzed in comparison with the A/He (highly susceptible) and AKR (resistant) lines of mice. Allelic variants of the K-Ras gene intron 2 in these lines have been determined. Susceptibility of the ICR mice was similar to that of the A mice, and intron 2 of the K-Ras ICR gene carried the 37-bp deletion analogous to that described in the A/He line. The DD mice intron 2 also contained the deletion, but despite the presence of the "susceptible" K-Ras allele, the DD/He mice were resistant to urethane induction of lung tumors. The CC57BR line carried the deletion and demonstrated relatively high susceptibility. Our findings indicate that the K-Ras gene may be important in the chemical induction of lung tumors.     

Comparative evaluation of the glycosaminoglycan composition in plasma membranes of normal and transformed mouse liver cells

Using electrophoresis in agarose gel, a comparative study of composition of membrane-bound glycosaminoglycans (GAG) from normal mouse liver cells and from o-aminoazatoluene-induced mouse hepatoma cells was carried out. Differences in the composition and localization of GAG were revealed. The plasma membrane fraction of hepatoma cells contained no GAG; the bulk of GAG (approximately 98%) was localized in the plasma membrane free fraction. Within this fraction GAG contained no heparan sulfates with a high electrophoretic mobility that were detected in plasma membranes of normal liver cells. The possible involvement of proteoglycans bound to cell surface in transmembrane signal transfer is discussed.     

Mutagenic activation and carcinogenicity of aminoazo dyes ortho-aminoazotoluene and 3′-methyl-4-dimethylaminoazobenzene in experiments on suckling mice

It is found that after administration of 3′-methyl-4-dimethylaminoazobenzene (3′-Me-DAB,) which was hepatocarcinogenic to rats, in suckling mice, the number of neoplastic lesions in the liver of mice was 3 times higher than after analogous administration of equimolar dose of ortho-aminoazotoluene (OAT)). However, in the Ames test (TA-98 strain of Salmonella typhimurium) with activation by hepatic enzymes (S-9 fraction) of both intact and Aroclor-1254-induced mice and rats OAT contributed by an order of magnitude to revertant colonies compared to 3′-Me-DAB. In vivo inhibition of sulfotransferase activity, the enzyme which catalyzes the final stage of the mutagenic activation of aminoazo dyes, had no effect on carcinogenicity of 3′-Me-DAB but more than 4 times elevated that of OAT. It was concluded that the mechanism of carcinogenic action of aminoazo dyes studied is not genotoxic and that the carcinogenic potential of OAT is lost in the process of mutagenic activation.     

Enhancer elements in the mouse CYP1A2 gene: a comparative sequencing among different inbred mouse strains

CYP1A2 expression is constitutively high in mouse liver and is well known for metabolizing several drugs and many procarcinogens to reactive intermediates that can cause toxicity or cancer. In the present study, the basal level of hepatic CYP1A2 activity was shown to vary among different inbred mouse strains. The highest methoxyresorufin-O-demethylase activity (261+/-52pmol/mgprotein/min) was registered in CC57BR and the lowest (82+/-11pmol/mgprotein/min) in C3H/a. We have tested the hypothesis that possible polymorphisms in regulatory elements in the 5'-upstream region of the mouse CYP1A2 gene could cause the differences in CYP1A2 enzyme activity among different inbred strains. We have performed a study on the CYP1A2 gene by sequencing the regulatory region from -4675 to -4204 where two enhancer elements were recently identified. The absence of mutation prescribing the phenotype in the CYP1A2 gene was found. The region studied seems to be a highly conserved in mice and not to be associated with interstrain differences in constitutive CYP1A2 enzyme activity.