Liver regeneration as influenced by the structure of aromatic and heterocyclic compounds.

The effect of aromatic hydrocarbons and derivatives and heterocyclic agents administered s.c. daily for the first 7 days or as dietary supplements was ascertained on the extent of liver regeneration in partially hepatectomized male rats over a period of 10 days. The monoalkylbenzenes proved ineffective by injection except for ethylbenzene and possibly n-propylbenzene and the introduction of the double or triple bond in the side-chain as exemplified by styrene and phenylacetylene, led to little change over the respective controls. A number of noncarcinogenic hydrocarbons accelerated the regenerative process but much higher s.c. dosages were required as compared to the carcinogenic hydrocarbons. As tested by the dietary route, the optimum effect among the phenylmethanes was reached with diphenylmethane, toluene, tri- and tetraphenylmethanes and the Sn analog, tin tetraphenyl being inactive. With the diets, carcinogens as BP or DBA at 0.10% were without effect whereas acenaphthene or fluoranthene at this level accelerated the regeneration. Although diets supplemented with anthracene or octahydroanthracene led to little change in liver increment, 9,10-dihydroanthracene, anthraquinone and anthrone comprised liver stimulants, an activity which did not extend to phenanthraquinone. Aniline and triphenylamine did not alter the control increment but diphenylamine was active as was also the case with o- and m-terphenyls, the p-isomer being ineffective. Although naphthalene lacked activity by either route, 1- and 2-phenylnaphthalenes proved stimulatory by injection and 1- and 2-naphthylamines, by diet. Among other derivatives, phenyl sulfide and its sulfoxide and sulfone were quite stimulatory in addition to heterocyclic S compound as benzothiophene, phenothiazine, phenoxathiin and thianthrene but not thianaphthene at the dietary levels screened. Several series were conducted with intact rats under the above conditions; ethyl-benzene and phenathrene injected s.c. at high levels did not alter the control dry- or wet liver-body weight ratios. The findings are summarized in Table 4.