title: Dacarbazine-induced immunogenicity of a murine leukemia is attenuated in cells transfected with mutated K-ras gene.
abstract: Strong immunogenicity is induced by antitumor triazene compounds in tumor cells through a mutagenic mechanism. A highly immunogenic <<D>> clone, isolated from a dacarbazine-treated L5178Y leukemia of DBA/2 mice, was transfected with K-ras mutated at codon 12 (i.e. ras(m12)). This transfected clone presents at least 2 mutations, one concerning K-ras gene, and the other affecting an unrelated gene, responsible for the generation of a highly immunogenic, MHC class I restricted non-self peptide. The results indicate that cells of <<D>> clone transfected with ras(m12) were less immunogenic than cells of the same origin transfected with the vector alone. Moreover, ras(m12)-transfected cells showed lower levels of H-2K(d) gene expression with respect to those detectable in control cells. In addition, in vivo and in vitro sensitization against <<D>> clone carrying mutated ras did not result in a strong cytotoxic T lymphocyte response against ras(m12)-transfected non immunogenic L5178y target cells. These preliminary results suggest that K-ras mutation could down-regulate the level of tumor immunogenicity, possibly acquired through a mutagenic process affecting other unrelated genes.
authors.affiliation: Dept. of Pharmacology, Chemotherapy and Toxicology, School of Medicine, State University of Milan, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Testorelli
authors.forename: S
authors.initials: S
authors.lastname: Bussini
authors.forename: R
authors.initials: R
authors.lastname: De Filippi
authors.forename: O
authors.initials: O
authors.lastname: Marelli
authors.forename: L
authors.initials: L
authors.lastname: Orlando
authors.forename: J W
authors.initials: JW
authors.lastname: Greiner
authors.forename: U
authors.initials: U
authors.lastname: Grohmann
authors.forename: L
authors.initials: L
authors.lastname: Tentori
authors.forename: A
authors.initials: A
authors.lastname: Giuliani
authors.forename: E
authors.initials: E
authors.lastname: Bonmassar
authors.forename: G
authors.initials: G
authors.lastname: Graziani
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003606:Dacarbazine / Q000494:pharmacology*; D011905:Genes, ras / Q000235:genetics / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D007940:Leukemia L5178 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D014162:Transfection / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D015395:Histocompatibility Antigens Class I; D003606:Dacarbazine