Open AccessLack of Chemoprevention Effects of the Monoterpene d ‐Limonene in a Rat Multi‐organ Carcinogenesis Model
Author(s) -
Kimura Juki,
Takahashi Satoru,
Ogiso Tadashi,
Yoshida Yasunori,
Akagi Keisuke,
Hasegawa Ryohei,
Kurata Mitsuo,
Hirose Masao,
Shirai Tomoyuki
Publication year - 1996
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1996.tb00264.x
Subject(s) - carcinogen , limonene , monoterpene , carcinogenesis , medicine , endocrinology , chemistry , nitrosamine , pharmacology , physiology , biology , biochemistry , cancer , food science , essential oil
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 α 2u ‐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.