Homocysteic acid, H03SCH2CH2CHNH2CO2H, promotes growth of hypophysectomized rats, assayed by observation of increased thickness of epiphyseal cartilage of the tibia and by observation of tail growth. Doses of homocysteic acid as low as 1 microgram per day for 4 days in the tibia assay and 2.5 milligrams per kilogram per day for 5 weeks in the tail assay were effective in promoting growth. Serum somatomedin activity, determined by the porcine cartilage disk assay, was also increased by homocysteic acid. These findings relate an area of sulfur amino acid metabolism to the physiological action of growth hormone, accelerated growth in homocystinuria, initiation of arteriosclerosis, and control of cellular growth.
Endothelial regeneration was studied in rabbit aorta after intra-arterial balloon catheterization. Most of the regenerated endothelium originated from existing branches which was assessed by the Evans-blue uptake pattern and confirmed by transmission and scanning electron microscopy. Glucocorticoid treatment enhanced re-endothelialization whereas hyperlipemic diet inhibited. Sera from minipigs fed an atherogenic diet consistently have less ability than sera from control pigs to stimulate in vitro the regeneration of wounded endothelium-like monolayers of 3T3-B cells. The deficiency is probably due to an inhibitor which appears and disappears with changes in the diet.
Since homocysteine metabolism is important in the control of normal and abnormal growth, three homocysteine derivatives were synthesized and tested for effects on the growth of transplanted murine adenocarcinoma. Arachidonoyl homocysteine thiolactone (HCT) amide decreased growth, and oleoyl HCT amide increased growth of the neoplasm. Pyridoxal HCT enamine decreased the growth of the neoplasm when given for 2 weeks prior to transplantation, but the compound had no effect when given after transplantation. The two inhibitory substances were tolerated well by normal mice except in high doses. These findings suggest an approach to prevention and therapy of human malignancy which utilizes homocysteine derivatives of normal biochemical constituents.
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