Possible tumor-initiating and -promoting activity of p-methylcatechol and methylhydroquinone in the pyloric mucosa of rat stomach.
The possible tumor-promoting and tumor-initiating activities of p-methylcatechol and methylhydroquinone in the pyloric mucosa of male F344 rats were studied. Ornithine decarboxylase (ODC) and replicative DNA synthesis (RDS) were used as markers of tumor promotion and DNA single strand scission and unscheduled DNA synthesis (UDS) as markers of tumor initiation. The compounds were administered by gastric intubation and results were compared with those after administration of catechol. p-Methylcatechol at doses of 60 to 180 mg/kg body weight dose-dependently induced up to 20-fold increase in ODC activity and 9-fold increase in RDS with maxima 24 h after its administration, but it did not induce significant DNA single strand scission or UDS. Methylhydroquinone at a dose of 200 mg/kg body weight induced up to 6-fold increase in ODC activity 24 h, and 5-fold increase in RDS 16 h after its administration, but the induction was not dose-dependent. At a dose of 200 mg/kg body weight it induced DNA single strand scission, but not UDS. These results and previous findings show that the possible tumor-promoting activities of catechol are several times higher than those of p-methylcatechol and 10 times higher than those of methylhydroquinone.
Furihata
C
C
Department of Molecular Oncology, University of Tokyo.
Oguchi
S
S
Matsushima
T
T
D000230:Adenocarcinoma / Q000139:chemically induced*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002396:Catechols / Q000633:toxicity*; D004249:DNA Damage; D004261:DNA Replication; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000187:drug effects*; D006873:Hydroquinones / Q000633:toxicity*; D008297:Male; D009955:Ornithine Decarboxylase / Q000096:biosynthesis; D011708:Pylorus / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D013274:Stomach Neoplasms / Q000139:chemically induced*; D013997:Time Factors
D002273:Carcinogens; D002396:Catechols; D004277:DNA, Single-Stranded; D006873:Hydroquinones; C018599:4-methylcatechol; C062397:2-methyl-1,4-hydroquinone; D009955:Ornithine Decarboxylase