title: Tumorigenic and molecular characterization of novel phorbol ester-resistant and -sensitive lines of mice.
abstract: Two outbred lines of CD-1 mice were developed using males and females in an initiation (dimethylbenz[a]anthracene; DMBA), promotion (12-O-tetradecanoylphorbol-13-acetate; TPA) challenge, posttumorigenesis breeding protocol. Our results indicate that the phorbol ester-sensitive (PESTI) line developed tumors at a rate 4.1 times faster than the CD-1 parental line, while the phorbol ester-resistant (PERTI) line developed tumors at a rate 36 times slower than the CD-1 parents. The average number of tumors per mouse reached levels of 27.5 at 12 wk in the PESTI line, 0.1 at 16 wk in the PERTI line, and 6.7 at 16 wk in the CD-1 line. Biochemical tests showed that the PESTI line had both a high basal level and an enhanced epidermal ornithine decarboxylase (E.C. 4.1.1.17) response to TPA, the latter being nine times that of the PERTI line at their maximum dosages. An autoradiographic analysis of in vivo epidermal cell protein phosphorylation indicated marked differences in basal protein phosphorylation profiles (with high phosphate incorporation, PERTI, 112.7, 95.5, 64.4, 40.8, 18.6, 17.4, and 12.3 kDa; PESTI, 64.4, 40.8, 31.8, and 12.3 kDa) as well as TPA-dependent changes in these profiles (difference from basal levels, PERTI, 31.8 and 12.8 kDa; PESTI, 139.6, 126.3, 37.2, and 18.6 kDa). These heterogeneous profiles indicate strong genetic segregation of these protein kinase C target substrates.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Southern Research Institute, Biochemical Carcinogenesis Section, Birmingham, Alabama 35255-5305.
authors.forename: F O
authors.initials: FO
authors.lastname: Cope
authors.forename: F J
authors.initials: FJ
authors.lastname: Wagner
authors.forename: T
authors.initials: T
authors.lastname: Conway
authors.forename: P D
authors.initials: PD
authors.lastname: Burns
authors.forename: D
authors.initials: D
authors.lastname: Johnston
authors.forename: P
authors.initials: P
authors.lastname: Murphy
authors.forename: G
authors.initials: G
authors.lastname: Triggs
authors.forename: J J
authors.initials: JJ
authors.lastname: Wille
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D001947:Breeding; D015197:Carcinogenicity Tests; D004351:Drug Resistance / Q000235:genetics; D004817:Epidermis / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics*; D009955:Ornithine Decarboxylase / Q000378:metabolism; D010703:Phorbol Esters / Q000633:toxicity*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D012878:Skin Neoplasms / Q000139:chemically induced; D013379:Substrate Specificity; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity
chemical_list: D010703:Phorbol Esters; D015127:9,10-Dimethyl-1,2-benzanthracene; D011493:Protein Kinase C; D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate