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White mural non-occlusive thrombus induced experimentally in the aortae of rabbits contains appreciable numbers of proliferating cells which contribute bulk and mass to the lesion. As these cells proliferate they produce appreciable amounts of collagen, elastin, and mucopolysaccharide which make the lesions resistant to dissolution by enzymes. In this study the proliferation of cells was monitored at serial time intervals up to 60 weeks by radioautography and chemical measurement of [H3]thymidine incorporation into DNA in order to determine over what time intervals appropriate antiproliferative drugs might be tested to arrest the growth of these cells. DPM [H3 thymidine incorporation into DNA became significant on Day 2, remained very high until Day 14 and then declined. The concentration of DNA per mg delipidated dry weight of thrombus between Day 0 and 4 was highly variable (6 to 60 μg/mg) due to the highly variable ratio of nucleated cells (monocytes and polymorphonuclear leukocytes) to fibrin and platelets. Between Day 0 and 4 weeks the DNA concentration became less variable as the polymorphsand monocytes were replaced by macrophages and spindle-shaped cells (10 to 20 yg/DNA per mg delipidated lesion). After 4 weeks DNA concentration declined continuously until by 60 weeks there was 2 ± 1 μg DNA/mg delipidated dry weight of lesion as it was diluted by collagen, elastin, and mucopolysaccharide. It is concluded that if antiproliferative drugs are to be used, they must be started as early as Day 2 and be maintained for at least 2 weeks.

Cell Proliferation and DNA Synthesis in Organizing White Mural Non-Occlusive Aortic Thrombus in Rabbits