Effect of diet-induced thiamine deficiency on visceral DNA synthesis and tissue composition

Abstract

The aims of this study were to assess the effect of dietary thiamine deficiency in rats on DNA synthesis and DNA, RNA and protein concentrations of heart, kidney, pancreas and liver. DNA synthesis rates, as determined by [ 14C]thymidine incorporation, declined in thiamine-deficient (TD) rats with neurologic signs to 36, 52, 32 and 64 per cent of pair-fed control (PFC) values in heart. kidney, pancreas and liver, respectively, 180 min after an intraperitoneal injection of the isotope (P < 0.05). Within 48 hr of thiamine repletion (“reversal”), DNA synthesis increased markedly in these organs of previously thiamine-depleted rats to 662, 3200, 307 and 1600 per cent of PFC values (P < 0.05). A 48-hr fast, in which TD and PFC food intake was restricted to 1 g/24 hr, after thiamine repletion, blunted the rebound in DNA synthesis. However, the DNA synthesis TD/PFC ratios in the reversed TD rats were still higher than during the symptomatic stage (P < 0.05), even in the presence of food restriction. Alterations in DNA labeling were not caused by the hypothermia which accompanies thiamine deficiency, and the 14C-label was located in the DNA thymine moiety in both TD and control groups. All organs, except the kidney, weighed less in symptomatic TD rats. and except for the heart, this effect was fully reversed within 48 hr of thiamine repletion. Total organ DNA was significantly reduced only in the liver, while DNA concentration (mg/g of tissue) in TD rats was significantly higher in heart, pancreas and liver. Protein concentration was generally comparable in TD and PFC tissues, and total RNA concentration was slightly lower only in the TD liver. In conclusion, dietary thiamine deficiency resulted in decreased DNA synthesis in every tissue studied and this appeared to involve only a small DNA pool. Since this type of experimental thiamine lack is accompanied by anorexia and weight loss which cannot be fully compensated by pair feeding, it is uncertain if the changes in DNA synthesis and tissue composition are due to thiamine deprivation per se or to secondary nutritional effects of thiamine deficiency such as impaired food utilization.