Inability of 4-Dimethylaminoazobenzene To Act as a Major

In the rat and other species “labile― methyl groups are essential to normal metabolism (5). These are methyl groups which are capable of be ing transferred in toto from one compound to an other by specific enzymes and enzyme cofactors. In the rat the major source of such groups is the diet, which may contain them in the form of such compounds as i@-methionine, choline, betaine, and possibly certain of the thetins. However, the tis sues of the rat also possess a limited ability to syn thesize labile methyl groups from one-carbon pre cursors related to formate and formaldehyde. While the methyl groups of compounds such as sarcosine and methanol (18) are not labile, they can act as minor secondary sources through oxida tive demethylation to these precursors. In the weanling rat the biosynthetic mechanism cannot supply the needs of rapid growth, and character istic lesions such as hemorrhagic degeneration of the kidneys result if sufficient dietary labile methyl groups are not available. The hepatocarcinogens related to 4-dimethyl aminoazobenzene (DAB) are characterized by the requirement of at least one N-methyl group for carcinogenicity (15). Since a chronic choline defi ciency also leads to the formation of liver tumors in the rat (1), it is important to decide to what ex tent the N-methyl groups in DAB are labile and whether or not DAB interferes with the normal metabolism of labile methyl groups. This paper is concerned with the first part of this question. Previous data from this laboratory (1@,13) have shown that in vivo only about 1 per cent of the methyl carbons of DAB and related dyes are found