PMID- 1579068
OWN - NLM
STAT- MEDLINE
DCOM- 19920610
LR  - 20231213
IS  - 0267-8357 (Print)
IS  - 0267-8357 (Linking)
VI  - 7
IP  - 2
DP  - 1992 Mar
TI  - Resistance to Pseudomonas toxin A: a sensitive marker to screen for mutagenic 
      substances using V79 cells.
PG  - 125-35
AB  - The goal of this study was the development of a mutagenicity assay in V79 cells 
      using Pseudomonas toxin A (PTA) as a selective agent and to compare it with the 
      V79/hypoxanthineguaninephosphoribosyl transferase (HGPT) assay. PTA inhibits 
      protein synthesis by covalently modifying elongation factor 2 (EF-2). Mutations 
      in the EF-2 gene, in genes responsible for the modification of EF-2, and also in 
      genes for the transport of the toxin into the cells, lead to PTA resistance. This 
      involvement of several genes might explain the relatively high spontaneous mean 
      mutation frequency of (122.7 +/- 38.8) x 10(-6) in growing cells (2 micrograms 
      PTA/ml) as compared with (3.97 +/- 4.68) x 10(-6) in the HGPRT test (10 
      micrograms thioguanine/ml), where only mutations in the HGPRT gene lead to 
      resistance. Methyl methanesulphonate, methyl nitroso urea and UV light were 
      directly mutagenic in the V79/PTA assay. Aflatoxin B1 was mutagenic in the 
      presence of an S9 mix. Benzidine, procarbazine, 2-acetylaminofluorene (2-AAF) and 
      4-acetylaminofluorene (4-AAF) were positive in the V79/PTA test when rat 
      hepatocytes were used for metabolic activation. Using cells treated together with 
      those used for the PTA assay, benzidine, 2-AAF and 4-AAF were negative in the 
      V79/HGPRT test, while procarbazine was found to be positive under these test 
      conditions. Hexamethyl phosphoramide (HMPA) was tested in the presence of rat 
      hepatocytes and was negative in both test systems. 
      Phorbol-12-myristate-13-acetate was highly cytotoxic, but did not induce 
      mutations at the PTA resistance loci. In conclusion, it was demonstrated that the 
      V79/PTA assay is an easy and sensitive method to screen for gene mutations in 
      mammalian cells.
FAU - Suter, W
AU  - Suter W
AD  - Sandoz Pharma Ltd, Drug Safety Assessment, Basle, Switzerland.
FAU - Negro, L
AU  - Negro L
FAU - Barrera, I
AU  - Barrera I
FAU - Schneider, B
AU  - Schneider B
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - England
TA  - Mutagenesis
JT  - Mutagenesis
JID - 8707812
RN  - 0 (Bacterial Toxins)
RN  - 0 (Biomarkers)
RN  - 0 (Exotoxins)
RN  - 0 (Virulence Factors)
RN  - 684-93-5 (Methylnitrosourea)
RN  - 9N2N2Y55MH (Aflatoxin B1)
RN  - AT5C31J09G (Methyl Methanesulfonate)
RN  - EC 2.4.2.- (ADP Ribose Transferases)
RN  - EC 2.4.2.8 (Hypoxanthine Phosphoribosyltransferase)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - *ADP Ribose Transferases
MH  - Aflatoxin B1/toxicity
MH  - Animals
MH  - *Bacterial Toxins
MH  - Biomarkers
MH  - Cell Line
MH  - Cricetinae
MH  - Drug Resistance
MH  - Exotoxins/*pharmacology
MH  - Hypoxanthine Phosphoribosyltransferase/pharmacology
MH  - Methyl Methanesulfonate/toxicity
MH  - Methylnitrosourea/toxicity
MH  - Mutagenicity Tests/*methods
MH  - Mutation
MH  - Tetradecanoylphorbol Acetate/toxicity
MH  - Ultraviolet Rays
MH  - *Virulence Factors
MH  - Pseudomonas aeruginosa Exotoxin A
EDAT- 1992/03/01 00:00
MHDA- 1992/03/01 00:01
CRDT- 1992/03/01 00:00
PHST- 1992/03/01 00:00 [pubmed]
PHST- 1992/03/01 00:01 [medline]
PHST- 1992/03/01 00:00 [entrez]
AID - 10.1093/mutage/7.2.125 [doi]
PST - ppublish
SO  - Mutagenesis. 1992 Mar;7(2):125-35. doi: 10.1093/mutage/7.2.125.