Lack of chemoprevention effects of the monoterpene d-limonene in a rat multi-organ carcinogenesis model.
Modifying effects of dietary administration of the monoterpene d-limonene were examined using a multi-organ carcinogenesis model. Groups of twenty F344 male rats were treated sequentially with N-diethylnitrosamine (DEN, i.p.), N-methyl-N-nitrosourea (MNU, i.p.), 1,2-dimethylhydrazine (DMH, s.c.), N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN, in drinking water) and dihydroxy-di-N-propylnitrosamine (DHPN, in drinking water) during the first 4 weeks (DMBDD treatment), and then d-limonene was administered in the diet, at the dose of 2.0, 1.0 or 0.5%. The maximal tolerable dose was 2.0% under the present conditions. Further groups were treated with DMBDD or 2.0% d-limonene alone as controls. All surviving animals were killed at week 28, and major organs were examined histopathologically for development of preneoplastic and neoplastic lesions. The incidences and/or multiplicities of renal atypical tubules and adenomas were increased in animals fed 2.0% d-limonene. The immunohistochemical reactivity for alpha2u-globulin in the proximal tubules was greater in rats fed d-limonene than in the carcinogen alone group. No enhancing or inhibitory effect was noted for tumor development in other organs. The present results indicate a lack of any chemopreventive effect of d-limonene in any organ of male rats under the present experimental conditions.
Kimura
J
J
First Department of Pathology, Nagoya City University Medical School, Nagoya, Japan.
Takahashi
S
S
Ogiso
T
T
Yoshida
Y
Y
Akagi
K
K
Hasegawa
R
R
Kurata
M
M
Hirose
M
M
Shirai
T
T
D019813:1,2-Dimethylhydrazine; D000236:Adenoma / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002085:Butylhydroxybutylnitrosamine / Q000008:administration & dosage; D002273:Carcinogens / Q000008:administration & dosage; D053138:Cyclohexenes; D004032:Diet; D004052:Diethylnitrosamine / Q000008:administration & dosage; D004127:Dimethylhydrazines; D007668:Kidney / Q000473:pathology; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D000077222:Limonene; D008297:Male; D008770:Methylnitrosourea / Q000008:administration & dosage; D009374:Neoplasms, Experimental / Q000139:chemically induced* / Q000517:prevention & control*; D009602:Nitrosamines / Q000008:administration & dosage; D051381:Rats; D011916:Rats, Inbred F344; D013729:Terpenes / Q000008:administration & dosage / Q000627:therapeutic use*
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D053138:Cyclohexenes; D004127:Dimethylhydrazines; D009602:Nitrosamines; D013729:Terpenes; D002085:Butylhydroxybutylnitrosamine; D004052:Diethylnitrosamine; C012457:diisopropanolnitrosamine; D008770:Methylnitrosourea; D000077222:Limonene; D019813:1,2-Dimethylhydrazine