Abstract
Earlier we demonstrated that short-term feeding of methapyrilene hydrochloride (MPH) and of a choline deficient (CD) diet to rats induced peroxidative damage of microsomal membrane lipids of liver cells. In the present study, we investigated whether a CD diet modifies the extent of MPH-induced lipid peroxidation and whether the modifications lead to changes in the initiating and promoting action of these agents using assays of the induction of gamma-glutamyltranspeptidase (GGT)-positive hepatocyte foci. Addition of 0.1% MPH to a CD diet enhanced the extent of microsomal lipid peroxidation induced by a CD diet alone. Feeding a choline supplemented (CS) or a CD diet containing 0.1% MPH for 2 weeks followed by 7 weeks promotion by a CD diet plus phenobarbital was ineffective in inducing GGT-positive foci. Feeding MPH in a CS or a CD diet for 4 weeks, however, resulted in the development of substantial numbers of GGT-positive foci. There was a 3 fold increase in the number of foci in rats initiated with a CD + MPH diet over that in rats initiated with a CS + MPH diet. 0.1% MPH in a CS diet or a CD diet exerted significant promotional effects on the induction of GGT-positive foci in rats initiated with a single injection of diethylnitrosamine. Addition of MPH to a CD diet was additive in inducing GGT-positive foci. The results suggest that lipid peroxidation of the liver may be involved in the carcinogenic and/or promoting effects of MPH and a CD diet.
Highlights
In confirming our earlier study (Perera et al, 1985b), feeding a choline deficient (CD) diet for 1 and 2 weeks showed the generation of diene conjugate
The difference spectrum of samples from rats fed a CD and choline supplemented (CS) diet is higher at 2 weeks than at 1 week
In the rats fed a CD+ methapyrilene hydrochloride (MPH) diet for 2 weeks, there is a broader peak of the absorption in the regions of 260-290nm (Figure 2b)
Summary
Male Sprague-Dawley rats (Zivic-Miller Laboratories, Allison Park, PA) weighing 170-180 g at the beginning of experiments, were used. They were housed individually in metal wire cages in a room which maintained 12 h light and dark cycles, a temperature 20+2°C and 50+10% relative humidity and were given Purina Chow (Ralston Purina, St. Louis, MO) and tap water ad libitum. The animals were acclimatized to the facility 10 days before the start of the experiments. Diets were stored at 4°C and the animals were provided with a fresh supply every 3 days. Body weights of animals were recorded at the beginning and at the termination of experiments. Thoroughly rinsed in the homogenizing buffer and subjected to the appropriate protocol
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