Immediate Effects of Carcinogens and Related Compounds on Pyridine Nucleotides

Abstract

TUMOUR growth is usually associated with low levels of pyridine nucleotides (PN)* (Glock and McLean, 1957; Jedeikin and Weinhouse, 1955). In addition, it was earlier shown from this laboratory that the levels and synthesis of pyridine nucleotides are also lowered in the host tissues of tumour bearing animals (Narurkar, Kumta and Sahasrabudhe, 1957 Narurkar and Sahasrabudhe, 1959). In all these instances, the host tissues showed a lowering of levels and synthesis of pyridine nucleotides. In view of the low levels of PN and the role PN play in energy production, a feed-back mechanism for regulation of normal growth was postulated (Sahasrabudhe, 1958). It was suggested that rapid cellular proliferation regulated its own growth through a self imposed curtailment in PN levels and therefore (though indirectly) of energy production. In malignancy, however, tumour continues to grow unrestrained in spite of the low levels of pyridine nucleotides, thus suggesting an existence of an alternative way of obtaining energy and a breakdown in the feed-back mechanism for regulation of normal growth. Since the diminished levels of PN are evident in almost every type of tumour, it was necessary to investigate whether the lowering in the pyridine nucleotides was in any way related to the factors responsible for the causation of malignant transformation. Alternatively the low PN levels may be the effect of malignant transformation, particularly since there is rapid nucleic acid synthesis. If the former possibility (i.e., the low PN levels as the causative factor of malignant transformation) be true, carcinogens should be able to produce some effects on PN levels long before malignancy sets in. This was investigated by studying the immediate or short term effects of some of the carcinogens and related compounds. MATERIALS AND METHODSWistar rats bred in our colony on stock diet were used in these experiments. The effect of the following substances was investigated: (1) p-dimethylaminoazobenzene (DAB or butter yellow), (2) 20-methylcholanthrene, (3) isoniazide, (4) semicarbazide, (5) urethane, (6) metatoluidine, (7) dimetheyl-p-phenylene-* The term " pyridine nucleotides" or " PN " denotes the sum total of DPN, DPNH TPN and TPNH.