Effects of aminothiols in 2-acetylaminofluorene-treated rats. I. Damage and repair of liver DNA, hyperplastic foci, and Zymbal gland tumors

One hundred and seventy-nine male Wistar rats were divided into 6 groups and fed with a standard diet supplemented with 0.05% 2-acetylaminofluorene (2AAF) and/or 0.1% glutathione (GSH) or N-acetyl-L-cysteine (NAC). Each treatment cycle lasted for 3 weeks, followed by 1 week of standard meal. After 4 cycles, survival was 100% in the 3 control groups, and 86.0, 100 and 91.7%, in the groups receiving 2AAF, 2AAF plus GSH, and 2AAF plus NAC, respectively. After an additional 4-8 weeks, all the 5 surviving rats fed with 2AAF exhibited deforming ear tumors, which on histological examination were classified as sebaceous squamocellular carcinomas of Zymbal glands. No such tumors were detectable in control groups, nor in the 16 surviving rats fed with 2AAF plus GSH or NAC. In the liver, 2AAF produced significant DNA damage at the 3rd week of each cycle, which was partially repaired during the week of standard meal feeding. Moreover, 2AAF determined the appearance of gamma-glutamyl transpeptidase-positive foci, which tended to increase with time both in number and in size. GSH and NAC exerted similar protective effects on these phenomena, but only at early stages of the experimental model used.