Vitamin B6and Biotin in Human Cancer Tissue*

Vitamin B6 and Biotin in Human Cancer Tissue* R. M. BALLANTYNEANDE.W MCHENRY

(From the Department of Public Health Nutrition, University of Toronto, Toronto 5, Canada)

A great deal of experimental work has been done tion, the same assay method could be used, simpli seeking some specific relation between the various fying the experimental procedure. vitamins and malignant neoplasms. The literature is extensive, but the diverse information is not EXPERIMENTAL readily fitted into a unified or consistent pattern All human neoplasms were obtained through for it is impossible to make extensive generaliza the cooperation of the Department of Surgical tions from the effects obtained with one type of Pathology, Toronto General Hospital, and the De tumor when the opposite effect may prevail with partment of Pathology, Toronto Western Hospi others. There are, however, three general ap tal. Sections of all tissues used for assay were made proaches to the problem and with these in mind in these respective departments and microscopic the scattered literature may be divided into first, examinations carried out. The diagnoses were re the relation of vitamins to the induction of tumors; ceived from these departments but no attempt was second, the relation of vitamins to the growth of made to determine the density of stroma, the pro tumors; and third, the vitamin content of tumors portion of malignant to normal cells or the amount as compared with that of normal tissues. Our in of necrosis present. All data represent the amounts vestigations fit into the third category but differ of the vitamins present per gram of the entire tu from most of the previous work in that we are mor mass. dealing with spontaneous human cancers, not an The tissue remaining after sections were made experimental type induced or transplanted in was available for assay and was prepared for deter animals. minations within six hours of removal in the case As vitamin B6 playst an important part in the of surgical specimens and within six hours of death transamination process it was felt that the amount in the case of autopsy specimens. A preliminary ex of this vitamin present in the neoplasm, compared periment was carried out in which it was shown with the amount present in the surrounding nor that there was no loss of vitamin B6 during a six mal tissue, might serve as an indication of the hour period following removal and thus the re amount of transamination taking place during suits represent the total amount of vitamin B6 neoplasia. In addition, the observation that the present in the tissue. Whenever possible vitamin feeding of a diet low in pyridoxine caused the rats estimations were carried out on surrounding nor to be more resistant to the induction of cancer mal tissue as well as on the neoplasm itself. (9, 10) and also caused a reduction of growth of The vitamin B6 and biotin content of the tu tumors aLready present (@,8) prompted the study mors was estimated microbiologically using the of the amount of vitamin B6 present in various method of Atkin et al. (1) utilizing Saccharomyces types of human neoplasms. carLibergensis. For the assay of biotin, pyridoxine A few studies were made on the biotin content hydrochloride was substituted for biotin in the of neoplasms, for biotin also seems to be related to basal medium and a 0.3 milligamma/cc. solution nitrogen metabolism as Winzler (l@) has indicated of crystalline biotin was used as a standard. With in his work with yeast. Biotin has been reported to this method the vitamin B5 content of 40 malig have a procarcinogenic effect on â€œbutteryellowâ€• nant tumors and @0samples of normal tissue was @ induction of tumors (5, 7) and has been reported determined as well as the biotin content of to affect the growth rate of tumors (3). In addi malignant tumors and 9 samples of normal tissue.

S This investigation was made possible by a grant from RESULTS the Ontario Cancer Treatment and Research Foundation for The vitamin B6 content of the neoplasms fell which thanks are expressed. within a range of 0.33 to 1.35 mcgm./gm., while t In this paper â€œvitaminB6â€•isused to include pyridoxine, pyridoxal and pyridoxamine, in accordance with nomenclature the values for surrounding normal tissue fell within approved by the American Institute of Nutrition on April 21, a much wider range from 0.@6 to 8.90 mcgm./gm. 1949. A similar situation was found with the biotin 689

690 Cancer Research

values, where the range for the neoplasms was cy the greater is the departure from normal. Neo @ O.0@2to0. 16 mcgm./gm. Figures 1 and depict the plasms are likely to be heterogeneous, being com average values for the vitamin content of the van posed of both cellular and non-cellular elements in ous neoplasms and their host tissues. varying proportions and in addition having vary ing degrees of central necrosis which would effect DISCUSSION the concentration values. A chemical similarity has been previously dem An examination of these results indicates that a onstrated, the first indication being reported by marked similarity of both vitamin B6 and biotin Con and Con in 19@5(4) when they found that the content exists among all examined types of neo lactic acid and sugar content of a sarcoma was plasms, and that this similarity is not evident very nearly the same as that of a carcinoma. among the normal host tissues. Not only are the Greenstein (6) has cited many instances where the vitalnin B6 values within a narrow range but the nearly uniform metabolic pattern of neoplasms, of different etiology and histogenesis, have been re ported. The similarity of the B vitamin content of @ â€”t@?Ti@@ neoplasms has been reported previously and our data, both quantitatively and with regard to uni formity in tumor tissue, are in general agreement with those found by Pollack, Taylor and Wil hams (11). In several reports in the literature regarding the vitamin content of neoplasms the comparison be tween normal and neoplastic tissue has been made on a percentage basis. A determination of this sort

@ 111i:i1lti1ii5iIAST . i.iarT sTasIs @- -- .s@ @.. _@ . . . â€¢ . @â€˜-@ VULVA 111515 VM(T I

FIG. I .â€”@itamiii B6 content of human tissues

values are similar to those for normal tissues hay ing a low vitamin B6 content, such as the mucosa of the gastro-intestinal tract. Other tissues having high values for their vitamin B6 content, such as liven, kidney and muscle, act as hosts for neo plasms which have small amounts of vitamin B6. In fact the vitamin B6 content of all malignant tu mors studied was found to have a standard devia @ BREAST LIME! 5T@IACft LISPS M@CL& OVARY PAJCUA3@ tion of 0.19 incgm./gm., whereas the correspond . AUTOPSY ing group of normal tissues varied oven such a wide range that the standard deviation could not be de FIG. 2.â€”Biotin content of human tissues termined. A similar observation was made when the biotin content of tumors and of normal tissues can be misleading as the foregoing results show no was considered. relationship between the neoplasms and their tis The standard deviation may be considered to be sues of origin. For example, if the vitamin B6 con too high to be of significance, but there are not tent of bowel carcinoma were compared with that only a large number of different types of tumors, of normal bowel mucosa, it would be regarded as but these tumors, even those of the same type, 10@ per cent of normal, whereas if the value for may vary considerably in the degree to which they liver carcinoma were compared with that of nor resemble or depart from the characteristics of nor ma! liver, it would be 11 per cent of normal. These mal tissue. In human neoplasms particularly, there are extreme examples but indicate the wide differ are elaborate gradations of malignancy and it has ence and the lack of quantitative relationship be l)CCflsaid that the greater the degree of malignan tween normal and tumor tissues.

SUMMARY Vol. II, in Vitamins and Cancer, p. 313. Academic Press, 1944. The vitamin B6 content of 40 human malignant 4. Corn, C. F., and C0RI, G. T. The Free Sugar, Lactic Acid tumors and @0samples of human normal tissue and Glycogen Content of Malignant Tumors. J. Biol. @ was determined, as well as the biotin content of Chem., 64:11â€”22, 192,5. malignant tumors and 9 samples of human normal 5. DU VIGNEAUD, V., SPANGLER, J. M., BUnK, D. , KENSLER. tissue. The vitamin B6 content of all malignant C. .1., and RHOADS,C. P. The Procarcinogenic Effect of Biotin in Butter Yellow Tumor Formation. Science, 96: tumors, irrespective of origin, fell within a narrow 174â€”176, 1942. - range of 0.33 to 1.35 mcgm./gm. This range was 6. GREENSTEIN,JJSSSEP.The Biochemistry of Cancer. Chap. similar to that of those normal tissues having a low VIII. Academic Press, 1947. vitamin B6 content. The various normal tissues 7. IL&nais, P. N., KRAHL, M. E., and Cww@, G. H. A. The studied had a wide range of values, from 0.@6 to Effect of Biotin upon p-dimethylaminoazobenzene Car cinogenesis. Cancer Research, 7: 176â€”177,1947. 8.90 mcgm./gm. The biotin content of all malig 8. KLINE, B. E., RUSCH, H. P., BATJMANN,C. A., and LAVIK, nant tumors fell within the range of 0.O@to 0.16 P. S. The Effect of Pyridoxine on Tumor Growth. Cancer mcgm./gm., while the normal tissues had a range Research,3:825â€”829,1943. of 0.03 to 0.66 mcgm./gm. The vitamin content of 9. MILLER, E. C., BAUMANN, C. A., and RuscH, H. P. Cer the neoplasms did not seem to bear any relation tam Effects of Dietary Pyridoxine and Casein on the Car to the vitamin content of the surrounding normal cinogenicity of p-dimethylaminoazobenzene. Cancer Re search, 5:713â€”716, 1945. tissue. 10. Mn@na,D.L., Mzu.mt, J. A., BAUMANN,C.A., and RuseH, REFERENCES H. P. The Effect of Pyridoxine and Other Vitamins on the 1. Ai,xn'a, L., SHULTZ,A. S., Wu@u@ss, W. L., and Fitay, Production of Liver Cancer with p-dimethylaminoazoben C. N. Yeast MicrobiologicalMethodsfor Determination of zene. Cancer Research, 3:296â€”302,1943. Vitamins; Pyridoxine. Indust. and Engin. Chem., Anal. 11. POLLACK,M.A., TAYLOR,A., and WIwAM5, R. B. Vita Ed., 15:141â€”144,1943. mins in Human, Rat and Mouse Neoplasms. University of 2. BiscHo@'r, F., INGRAHAM,L. P. , and Rupp, J. J. Influence Texas Publication, No. 4237:56â€”71,Oct. 1, 1942. of Vitamin B. and Pantothenic Acid on Growth of Sar 12. WINZLER,R.J., Buax, D., and DFVIGNEAUD,V.Biotin in coma 180.Arch. Path., 35:713â€”716,1943. Fermentation, Respiration, Growth and Nitrogen As 3. BURK, D., and Wmrzi.nit, R. J. Vitamins and Hormones, similation by Yeast. Arch. Biochem., 5:2.5â€”47,1944.

R. M. Ballantyne and E. W. McHenry

Cancer Res 1949;9:689-691.

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