Early liver alterations induced by the sex-dependent hepatocarcinogen beta-blocker ZAMI 1305.
Liver alterations occurring after 1, 6 or 10 days of treatment with the hepatocarcinogen beta-blocker DL-1-(2-nitro-3-methyl-phenoxy)-3-tert-butyl-amino-propan-2-ol (ZAMI 1305) were studied in male and female Wistar rats. In agreement with its sex-dependent oncogenicity, ZAMI 1305 administration causes DNA damage in the liver of the female but not of the male rat, with the only exception of 2 out of 4 males treated for 6 days. In female rat, the amount of DNA damage increases from 1 to 6 days of treatment, being unchanged at 10 days; a small portion of DNA is however damaged. ZAMI 1305 administration to female rat induces also: (i) an increase of the relative liver weight, of the DNA and RNA synthesizing activity; (ii) a decrease of the number of hepatocytes in mitosis; (iii) a minimal oval cell hyperplasia. When the same parameters were studied in ZAMI 1305-treated male rats, they were unaffected or changed to a less extent in respect to female rats.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002273:Carcinogens; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors; D014158:Transcription, Genetic / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D002273:Carcinogens; D011412:Propanolamines; C028475:ZAMI 1305; D001219:Aspartate Aminotransferases