Molecular analysis of formaldehyde-induced mutations in human lymphoblasts and E. coli
The molecular nature of formaldehyde (HCHO)-induced mutations was studied in both human lymphoblasts and E. coli. Thirty HPRT/sup -/ human lymphoblast colonies induced by eight repetitive 150 ..mu..M HCHO treatments were characterized by Southern blot analysis. Fourteen of these mutants (47%) had visible deletions of some or all of the X-linked HPRT bands, indicating that HCHO can induce large losses of DNA in human lymphoblasts. In E. coli., DNA alterations induced by HCHO were characterized with use of the xanthine guanine phosphoribosyl transferase (gpt) gene as the genetic target. Exposure of E. coli to 4 mM HCHO for 1 hr induced large insertions (41%), large deletions (18%), and point mutations (41%). Dideoxy DNA sequencing revealed that most of the point mutations were transversions at GC base pairs. In contrast, exposure of E. coli to 40 mM HCHO for 1 hr produced 92% point mutations, 62% of which were transitions at a single AT base pair in the gene. Therefore, HCHO is capable of producing different genetic alterations in E. coli at different concentrations, suggesting fundamental differences in the mutagenic mechanisms operating at the two concentrations used. Naked pSV2gpt plasmid DNA was exposed to 3.3 or 10 mM HCHO and transformed into E. coli. Most of the resulting mutations were frameshifts, again suggesting a different mutagenic mechanism.
- Research Organization:
- Chemical Industry Institute of Toxicology, Research Triangle Park, NC (USA)
- OSTI ID:
- 6615125
- Journal Information:
- Environ. Mol. Mutagen.; (United States), Vol. 12:2
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
FORMALDEHYDE
BIOLOGICAL EFFECTS
MUTATIONS
DNA SEQUENCING
ESCHERICHIA COLI
HYBRIDIZATION
LYMPHOCYTES
MAN
MOLECULAR BIOLOGY
PHOSPHORUS 32
ALDEHYDES
ANIMAL CELLS
ANIMALS
BACTERIA
BETA DECAY RADIOISOTOPES
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BODY FLUIDS
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MAMMALS
MATERIALS
MICROORGANISMS
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PHOSPHORUS ISOTOPES
PRIMATES
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STRUCTURAL CHEMICAL ANALYSIS
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