Neoplasm Studies X. The Effects in Tissue Culture of Some Split Products of p-Dimethyl- aminoazobenzene on Rat Liver Tumors*

Stevenson, Dobriner, and Rhoads (5) reported that p-dimethylaminoazobenzene when fed to rats is decomposed and metabolized to several simpler compounds. One of these split products, N,N-dimethylp-phenylenediamine, has been found by us ( i ) to be toxic to the glandular epithelium of the rat liver at concentrations of o.oooI M, while equivalent effects on the ductal epithelium were produced only with concentrations of o.oo2 to o.oo 4 M. The other compounds that may be derived from p-dimethylaminoazobenzene or that have been recovered from the urine of rats fed it are the following: aniline, p-aminophenol, N-acetyl-p-aminophenol, p-phenylenediamine, and N,N'-diacetyl-p-phenylenediamine (5). The tissue culture studies reported in this paper are on the effects of the nonacetylated split products mentioned above on normal rat liver and on liver tumors. The tissue cultures were prepared as described in the preceding report ( i ) , and when good growths were established comparable cultures were selected and exposed to a medium containing one of the split products. This was done by replacing a portion of the serum component in the medium with Tyrode solution containing the split product, the final concentration of the experimental compound being given below. Neither aniline hydrochloride, aniline sul]ate, nor p-aminophenol hydrochloride at concentrations of o.ooz M produces effects on wandering cells or on gland or duct epithelia, regardless of their source, i. e., norreal or neoplastic. This contrasts with our previous finding ( i ) that N,N-dimethyl-p-phenylenediamine at a concentration of o.ooi M destroys glandular epithelium but is relatively harmless to ductal epithelium. p-Phenylenediamine or p-phenylenediamine hydrochloride, at a concentration of o.ooi M, produces either