Weak yet distinct mutagenicity of acrylamide in mammalian cells.
BACKGROUND
Despite concern raised with the announcement that common heating processes such as frying introduce acrylamide, a known rodent carcinogen, into food, the mutagenicity of acrylamide in mammalian DNA is controversial.


METHODS
Big Blue mouse embryonic fibroblasts, which carry a lambda phage cII transgene, were treated with acrylamide. Formation of DNA adducts was determined by terminal transferase-dependent polymerase chain reaction. Mutational events were detected with a lambda phage-based mutagenesis assay and expressed as the frequency of the number of mutant cII plaques per total number of plaques screened. Mutations were confirmed by DNA sequence analysis. All statistical tests were two-sided.


RESULTS
In vitro treatment of the cells with acrylamide at millimolar concentrations induced DNA adducts along the cII gene. Treatment with acrylamide at micromolar concentrations increased the frequency of mutations in the cII gene up to twofold relative to control treatment (13.8 x 10(-5), 95% confidence interval [CI] = 12.3 to 15.3 x 10(-5) versus 6.9 x 10(-5), 95% CI = 6.5 to 7.3 x 10(-5), df = 2, 21; P<.001; ANOVA). The specificity of acrylamide in inducing cII gene mutations was shown by a statistically significantly different mutational spectrum from that in control-treated cells, with an excess of G --> C transversions and A --> G transitions (P =.024; Adams and Skopek test). Although some of the frequently mutated sites in the cII gene co-localized with sites of preferential DNA adduct formation, there was no direct relationship.


CONCLUSIONS
Acrylamide had distinct mutagenicity in transgenic mouse embryonic fibroblast cells, which might potentially be ascribed to its DNA adduct-inducing property. Whether acrylamide has the same effects on human cells is yet to be determined.
Besaratinia
Ahmad
A
Division of Biology, Beckman Research Institute of the City of Hope National Medical Center, Duarte, CA 91010, USA. ania@coh.org
Pfeifer
Gerd P
GP
D020106:Acrylamide / Q000009:adverse effects*; D000818:Animals; D002273:Carcinogens / Q000009:adverse effects*; D002478:Cells, Cultured / Q000187:drug effects; D003296:Cooking; D018736:DNA Adducts / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009152:Mutagenicity Tests; D009153:Mutagens / Q000009:adverse effects*; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
D002273:Carcinogens; D018736:DNA Adducts; D009153:Mutagens; D020106:Acrylamide