Enhancement of preneoplastic lesion yield by Chios Mastic Gum in a rat liver medium-term carcinogenesis bioassay.
The mastic (Pistacia lentiscus var. chia) tree is native throughout the Mediterranean region and has long proved a source of food additives and medical treatments. To investigate the modifying effects of Chios Mastic Gum on rat liver carcinogenesis, 6-week-old male F344 rats were subjected to the established rat liver medium-term carcinogenesis bioassay (Ito-test). At the commencement, rats (groups 1-4) were intraperitoneally injected with 200 mg/kg body weight of diethylnitrosamine (DEN). After two weeks, mastic was added to CRF (Charles River Formula)-1 powdered basal diet at doses of 0, 0.01, 0.1 and 1% in groups 1-4, respectively. At week 3, all rats were underwent two-thirds partial hepatectomy. The experiment was terminated at week 8. As results show, liver weights were significantly increased in a mastic dose-dependent manner among groups 1-4. The numbers (/cm(2)) and the areas (mm(2)/cm(2)) of glutathione S-transferase placental form (GST-P)-positive cell foci (>or=0.2 mm in diameter) were significantly increased in the DEN-1% group compared to the DEN-alone group, along with the average areas per foci and larger-sized foci (>or=0.4 mm). 5-Bromo-2'-deoxyuridine (BrdU)+GST-P double-immunohistochemistry showed the highest BrdU-labeling indices within GST-P foci in the DEN-1% group. 8-hydroxydeoxyguanosine (8-OHdG) levels in liver DNA did not vary, while real-time quantitative polymerase chain reaction (PCR) analysis of livers revealed many up- or down-regulated genes in the DEN-1% group. In conclusion, this is the first report to display a promotion potential of Chios Mastic Gum on the formation of preneoplastic lesions in the established rat liver medium-term carcinogenesis bioassay.
Doi
Kenichiro
K
Department of Pathology, Osaka City University Medical School, Abeno-ku, Osaka, Japan. kenchan@med.osaka-cu.ac.jp
Wei
Min
M
Kitano
Mitsuaki
M
Uematsu
Naomi
N
Inoue
Masayo
M
Wanibuchi
Hideki
H
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D015197:Carcinogenicity Tests; D004247:DNA / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004052:Diethylnitrosamine; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D051549:Glutathione S-Transferase pi / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D000069997:Mastic Resin; D019083:Mediterranean Region; D009929:Organ Size / Q000187:drug effects; D027927:Pistacia / Q000737:chemistry*; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000139:chemically induced*; D051381:Rats; D011916:Rats, Inbred F344; D012116:Resins, Plant / Q000008:administration & dosage / Q000633:toxicity*
D000069997:Mastic Resin; D012116:Resins, Plant; D004052:Diethylnitrosamine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D051549:Glutathione S-Transferase pi; C496558:Gstp1 protein, rat; D003849:Deoxyguanosine