The Carcinogenic Activities of N-hydroxy-2-acetylaminofluorene and Its Metal Chelates as a Function of Retention at the Injection Site.

The carcinogenic activities of s.c. administered N-hydroxy-2-acetylaminofluorene (N-hydroxy-AAF) and a variety of its metal chelates were investigated with reference to the time of exposure of the tissue to the compounds. No tumors were obtained at the sites of 4 injections of N-hydroxy-AAF (3.2 mg/injection), but 4 and 16 of 20 rats developed sarcomas at the sites of 8 and 16 injections, respectively. Ear duct carci nomas were also found in about one-half of the rats in each of the latter groups. An approximate correlation was noted between the retention of N-hydroxy-AAF ad ministered as the potassium salt or as various metal chelates and the incidence of sarcomas at the injection site. The nickelous, cobaltous, ferric, or cupric chelates induced moderate to high incidences of sarcomas with 1 or 4 injections ; in these cases one-half of the administered N-hydroxy-AAF was retained at the injection site for 4—50days. The manganous and zinc chelates and the potassium salt were less active at the injection site; the half-retention times for these derivatives ranged from 21 hr to 21 days. The comparable half-retention time for N-hydroxy-AAF was about 2 hr. Injection of the metal derivatives s.c. with short half-retention times resulted in higher incidences of mammary tumors than injection of the derivatives with half-retention times of 4 or more days. When administered p.o., the cupric chelate of N-hydroxy AAF induced the same spectrum of tumors as N-hydroxy-AAF, but the incidences were lower.