The Contents of Trichloroacetic Acid-soluble Sulphydryl Compounds and Ascorbic Acid in the Liver of Rats Fed Aminoazo Dyes: the Effect of a Single Large Dose of Dye

Abstract

FOLLOWING the original observation of Rapkine (1931) that the level of trichloroacetic acid (TCA)-soluble sulphydryl (SH) compounds in dividing sea urchin eggs fluctuated during cell division, considerable evidence has been accumulated to show that protein and non-protein SH groups play an important role in cell division (Needham, 1950 ;Barron, 1951 ;Mazia, 1954Mazia, , 1959Stern, 1959Stern, , 1960. Although it is not known how SH groups participate in this process, attempts have been made to relate carcinogenesis to a disturbance of this function. Thus Crabtree (1944, 1945, 1946) postulated that a primary carcinogenic disturbance is the binding of carcinogen to SH-containing cell constituents, and that anti-carcinogenic compounds which react with SH groups prevent this. On the other hand, Calcutt (1961) suggested that a rise in total SH level is essential for carcinogenesis and that anticarcinogenic substances inhibit this rise. Thus, the question of how SH groups take part in carcinogenesis has not been answered.The question of whether it is the protein or non-protein SH groups which play a role also remains open. This is not surprising since there is a lack of agreement by different workers on the effects of carcinogens on SH levels. In particular, apparently conflicting effects of hepatocarcinogens on the non-protein SH content of the liver have been reported. Among the workers who gave a single dose of carcinogen, Boyland and Mawson (1938) noted a rise in the TCA-soluble SH level in the liver of mice for more than 20 days following an intraperitoneal injection of 3,4: 5,6-dibenzocarbazole; Kennaway, Kennaway and Warren (1944) found that intraperitoneal injection of dimethylaminoazobenzene (DAB) into mice did not affect the metaphosphoric acid-soluble SH level; Roy, Miya and Carr (1958) observed that 5 hours after oral administration of DAB or /3-naphthylamine to rats the sulphosalicylic acid-soluble SH level in the liver was lower than in the controls; while Neish andRylett (1960, 1961) reported the appearance of an acidic thiol peptide in the liver of rats after an intraperitoneal injection of hepatocarcinogens, in contrast to non-carcinogenic compounds. In the case of continuous feeding of carcinogenic aminoazo dyes to rats, Roy, Miya andCarr (1957, 1958) reported slightly increased sulphosalicylic acid-soluble SH concentrations in the liver after 4 and 8 weeks followed by a depletion after 12 weeks if DAB was incorporated in a stock diet, and no increase if a low-protein diet was used; Fiala (1958) and Fiala and Fiala (1959) concluded that feeding 3'-methyl-DAB caused a late decrease of liver glutathione, but an increase of sulphosalicylic acid-soluble non-protein SH; and finally Calcutt, Doxey and Coates (1960) noted a slight SULPHYDRYL GROUPS AND ASCORBIC ACID increase of both metaphosphoric acid-soluble SH and total SH groups after feeding DAB, but in a later paper (1961) this effect was considered to be due to dietary factors rather than to the azo dye.To tell which effects of carcinogens are si...

Nitrosamine Metabolism in Protein-Deficient Weanling Rats during the Process of Repletion

“…The higher differential increase in liver size, its total microsomal protein content, and the overall body weight noted in the chronically protein-dependent animals, within 10 days of protein repletion, in comparison to the other experimental models (table 1), lend credence to the hypothesis of enzyme induc tion. The much higher content of glutathione (GSH), reported in livers of weanling rats chronically deprived of protein [12] in com parison to the low levels found after 'proteinfree' or acutely protein-deficient diets in adult rats [20][21][22], would also seem to ac count for the exceptionally high level of NDMA metabolism as well as support the concept of enzyme induction. In addition, the hypothesis of enzyme induction seems to coincide with an earlier finding [12] showing that chronically protein deprived male weanling Wistar rats, which were not sub jected to protein repletion, demethylated NDMA at rates comparable with their nor mal well-nourished counterparts.…”

A study of soluble protein and sulfhydryl levels in the rat liver during rapid normal and premalignant growth

“…Although the manner of involvement of the -SH groups in carcinogenesis is still a subject of hypothesis, hepatocarcinogenic substances, in general, bring about an increase in the -SH level in the liver. For example, a substantial increase of reduced glutathione in the liver was found at all weekly intervals up to 8 weeks in rats receiving 0-25 % DL-ethionine in the diet (Hsu and Geller, 1967); also, feeding a single dose of the azo carcinogens, 3'-methyl-4-dimethylaminoazobenzene or 4-dimethylaminoazobenzene, to rats causes a significant increase in trichloroacetic acid-soluble -SH groups in the liver after 40 hours (Dijkstra, 1964).…”

The Cell Surface Sulphydryl Content of Metastatic Variants of B16 Murine Melanoma

“…Furthermore, the non-protein thiol content is known to increase markedly in association with cellular transformation by carcinogenic polycyclic hydrocarbons and aminoazo dyes [7,9].…”