Revised rat multi-organ carcinogenesis bioassay for whole-body detection of chemopreventive agents: modifying potential of S-methylcysteine.
The DMBDD rat multi-organ carcinogenesis model based on two-stage carcinogenesis theory was revised to make more suitable assay system for detecting chemopreventive effects of chemical substances by increasing the doses of two carcinogens, 1,2-dimethylhydrazine dihydrochloride (DMH) and N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). The revised bioassay resulted in increasing preneoplastic or neoplastic lesions in the colon, urinary bladder and liver. S-Methylcysteine (SMC), a water-soluble organosulfur compound, was used as a test chemical in the new initiation regimen. Though SMC did not express clear-cut inhibitory effects in tumor levels, it showed modifying effects on the development of lung hyperplastic and colon preneoplastic lesions. In conclusion, the present model featuring high yields of preneoplastic and neoplastic lesions with low mortality in a short period (30 weeks), might be suitable for testing the efficacy of possible chemopreventive chemicals at the whole-body level.
Doi
Kenichiro
K
Department of Pathology, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno-Ku, Osaka 545-8585, Japan.
Wanibuchi
Hideki
H
Salim
Elsayed I
EI
Shen
Jun
J
Wei
Min
M
Mitsuhashi
Makoto
M
Kudoh
Shinzoh
S
Hirata
Kazuto
K
Fukushima
Shoji
S
D019813:1,2-Dimethylhydrazine / Q000633:toxicity; D000477:Alkylating Agents / Q000633:toxicity; D000818:Animals; D001681:Biological Assay / Q000379:methods*; D002273:Carcinogens / Q000633:toxicity; D018890:Chemoprevention / Q000379:methods*; D003106:Colon / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004052:Diethylnitrosamine / Q000633:toxicity; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D005982:Glutathione Transferase / Q000032:analysis; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology*; D009928:Organ Specificity / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344
D000477:Alkylating Agents; D002273:Carcinogens; D004052:Diethylnitrosamine; C008425:S-methylcysteine; D005982:Glutathione Transferase; D019813:1,2-Dimethylhydrazine; D003545:Cysteine