Promotion by dihydroxybenzene derivatives of N-methyl-N'-nitro-N-nitrosoguanidine-induced F344 rat forestomach and glandular stomach carcinogenesis.
Modifying effects of resorcinol, hydroquinone, p-tert-butylcatechol (PTBC), p-methylcatechol (PMC), and o-methylcatechol on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced forestomach and glandular stomach carcinogenesis were investigated in F344 rats. Groups of 15 to 16 male 6-wk-old animals were given a single intragastric administration of 150 mg/kg of body weight of MNNG and starting 1 wk later were administered powdered diet containing 0.8% resorcinol, 0.8% hydroquinone, 1.5% PTBC, 1.5% o-methylcatechol, 1.5% PMC, or basal diet alone for 51 wk. Additional groups of 10 to 15 rats each were treated with the phenolic compounds or received basal diet without prior carcinogen exposure. Histological examination after sacrifice at Wk 52 revealed that squamous cell carcinoma development in the forestomachs of rats treated with MNNG followed by PTBC (75%, P less than 0.001) or MNNG followed by PMC (100%, P less than 0.001) was significantly greater than in animals receiving MNNG alone (20%). Treatment with PMC alone also resulted in a 40% yield of papilloma. In the glandular stomach, incidences of adenomatous hyperplasias in rats treated with MNNG followed by PTBC (31.3%, P less than 0.05) or PMC (100%, P less than 0.001) and the incidence of adenocarcinomas in rats treated with MNNG followed by PMC (100%, P less than 0.001) were significantly higher than in controls. In addition, PMC alone induced a 100% yield of adenomatous hyperplasias and 6.7% of adenocarcinomas. Thus, the results demonstrated that PTBC and PMC treatment significantly enhances forestomach and glandular stomach carcinogenesis and that PMC itself may possess weak carcinogenic potential in these organs. The ortho-position appears to be important for this dihydroxybenzene activity.
Hirose
M
M
First Department of Pathology, Nagoya City University Medical School, Japan.
Yamaguchi
S
S
Fukushima
S
S
Hasegawa
R
R
Takahashi
S
S
Ito
N
N
D000230:Adenocarcinoma / Q000139:chemically induced* / Q000473:pathology; D000236:Adenoma / Q000139:chemically induced / Q000473:pathology; D000818:Animals; D006965:Hyperplasia; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000633:toxicity*; D010636:Phenols / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D013270:Stomach / Q000187:drug effects / Q000473:pathology*; D013274:Stomach Neoplasms / Q000139:chemically induced* / Q000473:pathology; D013329:Structure-Activity Relationship
D010636:Phenols; D008769:Methylnitronitrosoguanidine