title: Revised rat multi-organ carcinogenesis bioassay for whole-body detection of chemopreventive agents: modifying potential of S-methylcysteine.
abstract: 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.
authors.affiliation: Department of Pathology, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno-Ku, Osaka 545-8585, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Doi
authors.forename: Hideki
authors.initials: H
authors.lastname: Wanibuchi
authors.forename: Elsayed I
authors.initials: EI
authors.lastname: Salim
authors.forename: Jun
authors.initials: J
authors.lastname: Shen
authors.forename: Min
authors.initials: M
authors.lastname: Wei
authors.forename: Makoto
authors.initials: M
authors.lastname: Mitsuhashi
authors.forename: Shinzoh
authors.initials: S
authors.lastname: Kudoh
authors.forename: Kazuto
authors.initials: K
authors.lastname: Hirata
authors.forename: Shoji
authors.initials: S
authors.lastname: Fukushima
mesh_terms: 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
chemical_list: D000477:Alkylating Agents; D002273:Carcinogens; D004052:Diethylnitrosamine; C008425:S-methylcysteine; D005982:Glutathione Transferase; D019813:1,2-Dimethylhydrazine; D003545:Cysteine