title: High susceptibility of heterozygous (+/fa) lean Zucker rats to 7,12-dimethylbenz(a)anthracene-induced mammary carcinogenesis.
abstract: Susceptibility to 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinogenesis was investigated in lean Zucker (+/fa) rats carrying one mutated leptin receptor gene and wild-type controls (+/+). Rats with both genotypes were given a single DMBA administration and divided into two groups, one group was fed on basal diet mixed with 10% corn oil and the other was fed on basal diet alone. The minimum latency period of palpable carcinomas in +/fa rats of both groups was 8 weeks following DMBA treatment, in contrast to the 11-12 weeks in +/+. The incidence and multiplicity of carcinomas increased or showed a tendency for increase in the early stages in +/fa rats of both groups as compared to the +/+ counterparts. The volumes of carcinomas showed a tendency to increase in the corn oil diet groups of both genotypes. The major histopathological phenotype of carcinomas in all groups was well-differentiated without distinct atypia (multiplicity, 0.69-1.09/rat), but moderately/poorly differentiated carcinomas with atypia were also found, predominantly in +/fa rats (0.09-0.21). These latter tumors were characterized by elevated ERK activity but not estrogen receptor expression. Serum leptin concentrations in +/fa rats at 7 weeks of age were higher than those in +/+ and were elevated by the corn oil diet; however, no obvious change was detected in other serum parameters examined. In conclusion, +/fa rats proved more susceptible to DMBA-induced mammary carcinogenesis than +/+ controls, and hyperleptinemia was suggested to contribute to tumor growth as well as to susceptibility to tumorigenesis and more aggressive phenotypes in Zucker lean rats.
authors: Central Animal Division, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan. toimai@ncc.go.jp
authors: Toshio
authors: T
authors: Imai
authors: Young-Man
authors: YM
authors: Cho
authors: Mami
authors: M
authors: Takahashi
authors: Tsukasa
authors: T
authors: Kitahashi
authors: Shigeaki
authors: S
authors: Takami
authors: Akiyoshi
authors: A
authors: Nishikawa
authors: Kumiko
authors: K
authors: Ogawa
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D063646:Carcinogenesis / Q000187:drug effects* / Q000235:genetics* / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D003314:Corn Oil / Q000235:genetics / Q000378:metabolism; D004032:Diet / Q000379:methods; D004435:Eating / Q000187:drug effects / Q000235:genetics; D005260:Female; D006579:Heterozygote; D020738:Leptin / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011924:Rats, Zucker; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism; D015996:Survival Rate
chemical_list: D020738:Leptin; D011960:Receptors, Estrogen; D054411:Receptors, Leptin; D015127:9,10-Dimethyl-1,2-benzanthracene; D003314:Corn Oil