Effects of dosage and infusion time on the incorporation of 5‐fluorouracil into DNA and RNA of normal tissues and an adenocarcinoma transplanted to rat liver

Abstract

In a model of secondary liver cancer in Wistar rats the incorporation of 5-FUra into the acid soluble fraction, RNA, and DNA of several normal tissues and of an adenocarcinoma of the colon transplanted to the liver was determined; 300, 1,200 or 24,000 nmoles of 5-FUra were infused via the gastroduodenal artery for 0.5, 2, or 24 hr. The rats were killed 1.5, 3, or 24 hr after the beginning of the infusions. In general, higher doses resulted in a higher labelling. However, the ratio of incorporation into tumor RNA compared to normal tissue RNA was higher at the 1,200 than at the 24,000 nmole dosage. There was a decreased RNA/DNA ratio in the tumor at 24 hr after 24,000 nmoles of 5-FUra had been infused over 0.5 or 2 hr, indicating decreased synthesis and/or increased breakdown of RNA.

Incorporation of 5-fluorouracil into hepatoma and normal tissue RNA at protein depletion in the rat

“…Two days after catheter insertion the rats were infused via the hepatic artery over 2 hr with 1,200 nmole 5-FU + 0.25 mCi 5-[6-3 H]-FU (15.0 Ci/mmol, New England Nuclear, Boston, MA) in a volume of 1 ml, a dose suitable for experiments on uptake and distribution of 5-FU in tissues of rats weighing ∼200 g [7]. All rats were killed 1 hr after the end of the infusion around noon.…”

“…The tumor, most of the remainder of the liver, left kidney, spleen, and a piece of the terminal ileum, which was washed with cold saline, and femoral bone marrow were removed, immersed in liquid nitrogen, and stored at −70°C. The chemical analysis was performed as described previously [7].…”

Relation between the incorporation of 5‐fluorouracil into liver carcinoma and normal tissue RNA at hepatic arterial administration in the rat is altered by overnight starvation

“…After 1 day, 8 of the 16 rats were starved overnight. On the following morning the rats were infused over 2 hr with 1,200 nmol 5-FUra + 0.25 mCi 5-[6-3H]-FUra in a volume of 1 ml, a dose suitable for experiments on uptake and distribution of 5-FUra in tissues of rats weighing -200 g [7]. All rats were killed 1 hr after the end of the infusion.…”

“…The tumor, most of the remainder of the liver, the left kidney, and a piece of the terminal ileum which was washed with cold saline, and femoral bone marrow were removed, immersed in liquid nitrogen, and stored at -70°C. The chemical analysis was performed as described previously [ 7 ] .…”