Carcinogenecity 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 injected, i.p. 10 mumol/kg body weight (bwt) twice a week for 6 weeks, and 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 similarly injected at a dose of 100 mumol/kg bwt for comparison in female CD rats. Tumors of the liver, mammary gland and ear duct were produced in the female rats by these N-OH-AS derivatives. N-OH-AAS and N-OH-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 did the N-OH-ABP derivatives, even at 1/10 dose of the N-OH-ABP derivatives. In male CD rats, these N-OH-AS derivatives produced peritesticular mesothelioma and tumors of the pancreas and ear duct. N-OH-PAS also produced tumors of the small intestine and lung. The acetyl and propionyl derivatives were more carcinogenic than the formyl derivative of N-OH-AS for both male and female CD rats, suggesting that cytosolic acetyltransferases may be more important than the microsomal ones in activating these carcinogens.
Hirose
M
M
First Department of Pathology, Nagoya City University Medical School, Japan.
Shirai
T
T
Lee
M S
MS
Wang
C Y
CY
King
C M
CM
D000123:Acetyltransferases / Q000378:metabolism; D000577:Amides / Q000378:metabolism; D000818:Animals; D001711:Biotransformation; D001835:Body Weight / Q000187:drug effects; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D005260:Female; D008297:Male; D009374:Neoplasms, Experimental / Q000139:chemically induced; D051381:Rats; D013267:Stilbenes / Q000633:toxicity*
D000577:Amides; D002273:Carcinogens; D013267:Stilbenes; D000123:Acetyltransferases