In vitro mutagenicity of the plasmacytomagenic agent pristane (2,6,10,14-tetramethylpentadecane).
Pristane is known to induce a distinct type of B-cell-derived malignant lymphoma, plasmacytoma, after administration into the peritoneal cavity of genetically susceptible BALB/cAnPt mice. Since the mechanism of pristane-induced plasmacytoma development is poorly understood, we chose to examine the possibility that pristane is mutagenic in rodent cells and decided to use bacteriophage lambda-derived lacI/lacZ genes as target/reporter to quantitate mutagenesis. Here we show that in vitro exposure to micromolar amounts of pristane, delivered as an inclusion complex with beta-cyclodextrin, resulted in 1.7-fold and 6.2-fold increases of mutant frequencies over controls in a cell line of rat fibroblasts and primary mouse B lymphocytes, respectively. We conclude that pristane can be mutagenic to mammalian cells, yet are currently unable to explain the mechanism of mutagenicity. It is suggested that B-cell mutagenesis contributes to the plasmacytomagenic activity of pristane in vivo.
Felix
K
K
Institut für Klinische Molekularbiologie and Tumorgenetik, München, Germany. felixk@dc37a.nci.nih.gov
Potter
M
M
Bornkamm
G W
GW
Janz
S
S
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects; D001483:Base Sequence; D002273:Carcinogens / Q000633:toxicity*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects; D051379:Mice; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D013729:Terpenes / Q000633:toxicity*
D002273:Carcinogens; D009153:Mutagens; D013729:Terpenes; C009042:pristane