Stimulation of Diethylnitrosamine Metabolism Reduces Its General Toxic and Hepatocarcinogenic Effects.

The general toxic and hepatocarcinogenic effects of diethylnitrosamine after stimulation of its metabolism with 1,4-bis[2-(3,5-dichloropyridyloxy)]-benzene (TCPOBOP) were studied. The hydroxylating activity of liver microsomes of C57Bl/6Mv mice towards p-nitrophenol increased more than 4-fold 3 days after injection of TCPOBOP. Injection of diethylnitrosamine 3 days after TCPOBOP caused a lesser body weight loss and decrease of food consumption in C57Bl/6Mv mice than in response to diethylnitrosamine without preinduction.

[Effect of Hepatic P450 2e1 Activity Modulation on the Toxicity and Carcinogenicity of Diethylnitrosamine in Mice].

In this paper, the biological effects of diethylnitrosamine have been studied under controlled conditions of its metabolism in mice of different ages. The data presented indicate that diethylnitrosamine in a non-metabolized form exerts general toxic and hepatocarcinogenic effects while alkylating agents of this compound produce toxic liver injury. To our knowledge, the data presented impel to revise the general notion of an exceptional role of mutagenic activation in the carcinogenic effect of chemicals.

Suppression of sulfoconjugation reduces the protective effect of ortho-aminoazotoluene on hepatocarcinogenesis induced by diethylnitrosamine in mice.

The effects of ortho-aminoazotoluene on carcinogenic activity of diethylnitrosamine were studied in CBA and ICR mice. Injection of ortho-aminoazotoluene before and after diethylnitrosamine led to a significant reduction of its anticarcinogenic effect, judging from significantly lower level of liver tumors. Pentachlorophenol, inhibitor of sulfotransferase (catalyzing the terminal stage of ortho-aminoazotoluene metabolic activity), stimulated its carcinogenic effect on mouse liver.

OAT and 3'MeDAB azo compounds similarly cause liver tumors in GR mice, but differently modify activities of FoxA transcription factors.

Transcription factors of the FoxA family (forkhead box A) regulate cell metabolism and differentiation and maintain specificity of liver cell proteome and phenotype of mature hepatocytes. The relationship between hepatocarcinogenicity of azo compounds o-aminoazotoluene (OAT) and 3'-methyl-4-dimethylaminobenzene (3'MeDAB) for GR mice and one of the early events, modulation of the DNA-binding activity of FoxA transcription factor, was studied. Single injection of 3'MeDAB to 12-day-old mice caused liver tumors in 100% males and females similarly as OAT, a well-known mouse hepatocarcinogene.

Depressive-like psychoemotional state versus acute stresses enhances Lewis lung carcinoma metastasis in C57BL/6J mice.

Aim: The effect of a depression-like status formed by chronic stress on the 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.

Methods: 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.