Tumor growth and the incorporation of [3H]
thymidine into
tumor DNA in vivo are increased about 3 times in adult rats (greater than 250 g) after 1 to 2 days of
starvation or the induction of diabetes with
streptozotocin. These
tumor growth responses require
hyperlipemia and are reversed by refeeding or
insulin treatment, respectively. They do not occur in young
tumor-bearing rats (less than about 150 g) that lack appreciable fat stores. A direct relationship between the increased rates of both [3H]
thymidine incorporation and
tumor growth and host
hyperlipemia suggests that
tumor cell renewal in vivo in fed rats is limited by substances that are present in hyperlipemic blood. In this study we used a procedure for perfusion of solid
tumors in situ to measure the sensitivity of
tumor [3H]
thymidine incorporation to hyperlipemic blood and to identify the rate-limiting substances. Tissue-isolated Morris
hepatomas (7288CTC) growing in young or adult Buffalo rats were perfused with blood from donor rats. Hyperlipemic blood for perfusion was obtained from 2-day starved
tumor-bearing (Buffalo) or non-
tumor-bearing (Buffalo or Lewis) rats. At the end of the perfusions the
tumors were labeled with a pulse of [3H]
thymidine (2 microCi/g estimated
tumor wet weight). [3H]
Thymidine incorporation in
tumors growing in fed adult rats was increased from 80 +/- 5 (SD) dpm/micrograms
DNA at zero time (before perfusion) to 209 +/- 9 dpm/micrograms
DNA (n = 3) after perfusion for 3 h.
Tumors growing in fed or starved young rats showed similar responses, and hyperlipemic blood from non-
tumor-bearing rats was as effective as hyperlipemic blood from
tumor-bearing rats. Perfusion of
tumors growing in starved rats with normolipemic blood from fed adult rats decreased [3H]
thymidine incorporation from 211 +/- 13 dpm/micrograms
DNA before perfusion to 68 +/- 9 dpm/micrograms
DNA (n = 3) after perfusion for 3 h. Cells, plasma, and plasma subfractions from hyperlipemic blood were reconstituted to whole blood using plasma, cells, and whole blood, respectively, from fed rats and the mixtures were perfused into
tumors growing in fed adult rats. Mixtures containing hyperlipemic plasma,
lipid extracts (
ethanol:
acetone, 1:1) of hyperlipemic plasma, or
albumin from hyperlipemic plasma increased
tumor [3H]
thymidine incorporation.
Free fatty acid concentrations were increased about five times in hyperlipemic plasma and perfusion of
tumors with normolipemic blood containing added linoleic and
arachidonic acids increased [3H]
thymidine incorporation. Blood mixtures containing palmitic, stearic, and
oleic acids were inactive.(ABSTRACT TRUNCATED AT 400 WORDS)