CARCINOGENICITY OF THE N-ACYL DERIVATIVES OF N-HYDROXY-TRANS-4-AMINOSTILBENE IN CD RATS

Carcinogenicities of the N-formyl (N-OH-FAS), N-acetyl (N-OH-AAS) and N-propionyl (N-OH-PAS) derivatives of N-hydroxy-trans-4-aminostilbene (N-OH-AS) were investigated in male and female CD rats. They were inje cted, i.p. 10 mu mol/kg body weight (bwt) twice a week for 6 weeks, an d they were killed at the end of 62 weeks. The N-formyl, N-acetyl and N-propionyl derivatives of N-hydroxy-4-aminobiphenyl (N-OH-ABP) were s imilarly injected at a dose of 100 mu mol/kg bwt for comparison in fem ale CD rats. Tumors of the liver, mammary gland and ear duct were prod uced in the female rats by these N-OH-AS derivatives. N-OH-AAS and N-O H-PAS were more active in the induction of mammary and ear duct tumors than N-OH-FAS. These N-OH-AS derivatives produced more tumors than di d the N-OH-ABP derivatives, even at 1/10 dose of the N-OH-ABP derivati ves. In male CD rats, these N-OH-AS derivatives produced peritesticula r mesothelioma and tumors of the pancreas and ear duct. N-OH-PAS also produced tumors of the small intestine and lung. The acetyl and propio nyl derivatives were more carcinogenic than the formyl derivative of N -OH-AS for both male and female CD rats, suggesting that cytosolic ace tyltransferases may be more important than the microsomal ones in acti vating these carcinogens. (C) 1997 Elsevier Science Ireland Ltd.