UBC Theses and Dissertations
Biochemical studies of chloroleukemia in female Sprague-Dawley rats Lee, Lilian Miu Yee
The chloroleukemia (chloroma) in the Cancer Research Centre, U.B.C. could be transplanted into adult Sprague-Dawley rats with tumour homogenates, whole blood and ascitic fluid containing intact cells. Cell-free filtrates of the ascitic fluid did not give rise to tumours. It was considered probable that intact cells were required for the transmission of this leukemia. The present study showed that there was a 'latent period' of 10 to 12 days after which the chloroma grew rapidly until the death of the animal (ca 27 days). The tumour contained substantial amounts of free protoporphyrin and had high myeloperoxidase activity. The protoporphyrin concentration increased markedly and continuously with the age of the tumour but its rate of synthesis (from glycine-2-C¹⁴) declined after the 19th day, i.e..protoporphyrin accumulated in the tumour. The myeloperoxidase activity increased between the 13th and 15th day after transplantation and thereafter fell sharply. The effect of two drugs - Vinblastine (VLB) and 3,5-dicarbethoxy-1,4-dihydrocollidine (DDC) on certain aspects of the biosynthetic activity of this particular adult chloroma was investigated. VLB inhibited the incorporation of glycine-2-C¹⁴ into both RNA and protein earlier and to a greater extent than into the DNA and protoporphyrin. This tumour, although of hematopoietic origin, did not therefore show the high sensitivity of normal bone marrow to VLB. DDC markedly increased the Δ -aminolevulinic acid synthetase activity and protoporphyrin concentration in the liver of rats but had no effect on the tumour protoporphyrin synthesis although there was more than a 20-fold increase in Δ -aminolevulinic acid synthetase activity. It was suggested therefore that the enzyme Δ-aminolevulinic acid synthetase may be rate-limiting in the liver but not in the tumour. In the course of the present work, an improved method for the separation of porphyrin esters based on partition chromatography on alumina was developed.
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