Inducible mutagenesis in TEPC 2372, a mouse plasmacytoma cell line that harbors the transgenic shuttle vector lambdaLIZ.
The plasmacytoma cell line, TEPC 2372, was derived from a malignant plasma cell tumor that developed in the peritoneal cavity of a BALB/c mouse that harbored the transgenic shuttle vector for the assessment of mutagenesis in vivo, lambdaLIZ. TEPC 2372 was found to display the typical features of a BALB/c plasmacytoma. It consisted of pleomorphic plasma cells that secreted a monoclonal immunoglobulin (IgG2b/lambda), was initially dependent on the presence of IL-6 to grow in cell culture, contained a hyperdiploid chromosome complement with a tendency to undergo tetraploidization, and harbored a constitutively active c-myc gene by virtue of a T(6;15) chromosomal translocation. TEPC 2372 was further characterized by the ability to respond to in vitro exposure with 4-NQO (4-nitroquinoline-1-oxide), an oxidative model mutagen, with a vigorous dose-dependent increase in mutagenesis that peaked at a 7.85-fold elevation of mutant rates in lambdaLIZ when compared to background mutant rates in untreated controls. Cotreatment with 4-NQO and BSO (buthionine sulfoximine), a glutathione-depleting compound that causes endogenous oxidative stress, resulted in a 9.03-fold increase in the mutant frequency in lambdaLIZ. These results demonstrated that TEPC 2372, the malignant plasma cell counterpart of the lambdaLIZ-based in vivo mutagenesis assay, may be useful as an in vitro reference point for the further elucidation of oxidative mutagenesis in lymphoid tissues.
Felix
K
K
Laboratory of Genetics, DBS, NCI, Building 37, Room 2B10, Bethesda, MD 20892-4255, USA. felixk@dc37a.nci.nih.gov
Kovalchuk
A L
AL
Park
S S
SS
Coleman
A E
AE
Ramsay
E S
ES
Qian
M
M
Kelliher
K A
KA
Jones
G M
GM
Ried
T
T
Bornkamm
G W
GW
Janz
S
S
D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage; D020732:Cytogenetic Analysis; D016259:Genes, myc / Q000235:genetics; D005822:Genetic Vectors / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016296:Mutagenesis / Q000187:drug effects*; D009152:Mutagenicity Tests; D010954:Plasmacytoma / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D013729:Terpenes / Q000008:administration & dosage; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D002273:Carcinogens; D012333:RNA, Messenger; D013729:Terpenes; C009042:pristane