530 IX. CAROTENOIDS AND VITAMINS A 



rats "with spontaneous tumors, as well as of those with tumors due to 

 methylcholanthrene, contained more vitamin A than did livers in which no 

 tumor formation had taken place. 



A problem exists as to the fate of the vitamin A which disappears from 

 the liver after the injection of 1,2,5,6-dibenzanthracene. The hydrocarbon 

 might promote the excretion of vitamin A, it might increase the rate of de- 

 struction of vitamin A, or it might alter the distribution of vitamin A be- 

 tween the liver and other organs. The first of these possibilities cannot be 

 accepted as the explanation, since Goerner and Goerner'"'^ found that no 

 vitamin A was excreted in the urine after the injection of the carcinogen. 

 Moreover, Baumann et alJ^^ were unable to detect vitamin A in the com- 

 bined excreta of rats receiving 1,2,5,6-dibenzanthracene. There are no 

 data indicating that the second possibility, i.e., an increased rate of de- 

 struction of liver \dtamin A, may partly account for its effect. However, 

 Baumann and co-workers''"^ reported that the third possibility cited above 

 can be readily demonstrated experimentally. Thus, it was shown that, 

 coincident \\dth the reduction in liver vitamin A following the injection of 

 dibenzanthracene, there was a concomitant rise in the vitamin A content of 

 the kidneys. Methylcholanthrene was found to promote a similar shift 

 of vitamin A from the liver to the kidneys. '^"^ Although as much as 50% 

 of the total vitamin A of rats injected with dibenzanthracene was found in 

 the kidneys (in contrast with only 5% in normal rats) , the increased quan- 

 tity of \'itamin A stored in the kidney accounted for only 10% of that 

 which had left the liver. The best explanation for the decreased capacity 

 of the liver to store vitamin A under these conditions is that the liver 

 component to which vitamin A is attached is altered or missing; presum- 

 ably this component is a protein (see page 520) . 



h. Miscellaneous Factors Affecting Vitamin A Storage. In addition to 

 dibenzanthracene, a number of other drugs have been found to cause a 

 depletion in hepatic vitamin A. Thus, drugs which cause a blocking of the 

 reticuloendothelial system, such as thorotrast,''''' phenylhydrazine,'"^ or 

 bismuth,'' ^^ reduce the storage of vitamin A in the liver. The antimalarial 

 drug atabrine, in addition to reducing the rate of absorption of carotene 

 and of \dtamin A, was showni by Guggenheim^^ to decrease the capacity of 

 the liver to store vitamin A. 



Alcohol also inhibits the vitamin A storage in the liver,''^' although the 



™3 C. A. Baumann, E. G. Foster, and P. R. Moore, /. Biol. Chem., 142, 597-608 (1942). 

 "» F. Lasch and D. Roller, Klin. Wochschr., 15, 16.36-1637 (1936). 

 "' H. Wendt and D. Konig, Klin. Wochschr., 16, 1253-1254 (1937). 

 "2 I. Ikegaki, Z. Vitaminforsch., 7, 113-118 (1938). 



