The activity of S-adenosyl-L-methionine Decarboxylase (E. C. 4.1.1.50) was measured in two different normal and five different tumorous mouse mananary tissue samples. The soluble fraction was assayed for SAM decarboxylase activity using 14COOHlabeled SAM as the substrate. The amount of 14002 evolved was measured using a liquid scintillation counter.There was a significant elevation of SAM decarboxylase activity in the tumor sample group. The activities of the tumor tissue was x = 15.62 and SD = 8.24. The activity in the normal samples was too low to measure:These results suggest an increase in not only SAM decarboxylase activity, but also in the levels of spermidine and spermine. These increases are characteristics of cancer cells and may result in changes in enzyme activities and membrane phospholipid composition.

No description available.

The basis for the species difference between B6C3F1 mice (susceptible) and Fischer 344 rats (resistant) to 4- vinylcyclohexene (VcH)-induced ovarian tumorigenicity was investigated. Greater than 95% of a single oral 400 mg/kg dose of [¹⁴C]VCH was eliminated in 48 hr by mice and rats. Approximately 50-60% of the administered dose was excreted in the urine, while the remaining 30-40% of the dose was expired as organically soluble radioactivity. VCH-treated mice had dramatically higher blood concentrations of the VCH metabolite VCH-1,2-epoxide compared to VCH-treated rats. Furthermore, mouse hepatic microsomes catalyzed the conversion of VCH to VCH-1,2-epoxide at greater rates than rat hepatic microsomes. The destruction of oocytes was used as an index of ovarian toxicity to compare the potency of VCH and VCH epoxides in the mouse and rat. VCH markedly reduced the number of small oocytes in mice while no detectable change in oocyte number occurred in rats. Epoxide metabolites of VCH destroyed oocytes in both species at lower doses than VCH. Inhibition of VCH epoxidation reduced VCH-1,2-epoxide blood levels and partially protected mice from VCH-induced ovarian toxicity. Thus, the conversion of VCH to epoxides and the subsequent destruction of oocytes are critical steps in the induction of ovarian tumors by VCH. Rats may be resistant because the amount of VCH converted to epoxides is insufficient to destroy oocytes. The biochemical basis for the species difference in the rate of VCH epoxidation by hepatic microsomes from mice and rats was investigated. studies using inducers and inhibitors of certain cytochrome(s) P450 showed that hepatic microsomes of female mice perform VCH epoxidation at greater rates than rats because of the constitutive expression of P450 IIA and lIB forms. Hepatic microsomes of human females perform VCH epoxidation at lower rates than rats. This suggests that if the rate of epoxidation of VCH by the liver is the most important factor determining susceptibility to VCH toxicity then the rat may better model the response of humans exposed to VCH than mice.

published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / Surgery / Doctoral / Doctor of Philosophy

The activities of phosphohexose isomerase (EC. 5.3.1.9), isocitrate dehydrogenase (EC. 1.1.1.42) and lactate dehydrogenase (EC. 1.1.1.27) were measured in 14 normal and 21 tumorous mouse mammary tissue samples. Methods of tissue extraction and activity determination in this study employed equipment found in most clinical laboratories.For each of the three enzymes there was a statistically significant (p <.05) elevation of the tumor sample group's activities. The activities of the normal tissues were: PHI x = 9.6 and SD = 4.6, ICD x = 13.2 and SD = 5.3, and IDH x = 10.9 and SD = 5.3. The activities of the tumorous tissues were: PHI x = 55.2 and SD = 29.9, ICD x = 40.5 and SD = 23.8, and IDH x = 55.8 and SD = 31.4.Using values of 20, 27, and 21 for the upper limit of normal activity (x + 2SD) for PHI, ICD, and LDH respectively, the tissue samples can be divided into normal and tumorous groups with l00% sensitivity and 85% specificity.Ball State UniversityMuncie, IN 47306

published_or_final_version / Anatomy / Master / Master of Philosophy

published_or_final_version / Pathology / Master / Master of Philosophy

published_or_final_version / Pathology / Master / Master of Philosophy

Brain metastasis is a frequent occurrence in cancer patients and carries a high mortality rate. The incidence of brain metastasis is on the rise, highlighting the need for improved therapeutic intervention. Immune cells have been shown to promote disseminated tumour cells to colonise the lung and liver. Therefore, we aim to determine whether immune cells also facilitate brain metastasis by describing the host immune response to tumour cells attached to the brain vasculature. We developed a model of brain metastasis by using ultrasound guidance to perform intracardiac injection of tumour cells. Using this method, we identified highly and weakly brain metastatic cell lines. To understand how cancer cells develop into brain metastases, we analysed brains harvested 4 h- 14 d after tumour injections. At 4 h after intracardiac injection, only cell lines that developed into brain metastases were found adhered to the brain vasculature in high numbers. A small number of arrested tumour cells clustered with CD45⁺ immune cells. These tumour-CD45 clusters persisted over time whilst the frequency of solitary tumour cells declined. Tumour-associated CD45⁺ immune cells were identified to be Ly6G⁺Gr-1⁺CD11c⁻ myeloid cells. Considerably more tumour-CD45⁺ immune cell clusters were found within the brain vasculature when tumour cells were injected into mice bearing a primary tumour. Increased tumour-CD45⁺ immune cells clusters correlated with an increased number of brain metastases in the same group of mice. We also found a positive association between increased tumour-immune clusters and levels of tumour and host derived G-CSF. To establish a causal relationship between tumour cell-CD45 clusters and metastases, we developed an experimental setup for transcranial imaging. Our results suggest that tumour recruited immune cells may promote tumour cell colonisation of the brain and provides a framework for further investigation.