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Genotoxicity and genotoxic enhancing effect of tetrandrine in Salmonella typhimurium.

Authors
Whong-Z; Lu-H; Stewart-JD; Jiang-X; Ong-T
Source
Mutat Res 1989 Mar; 222(3):237-244
NIOSHTIC No.
00187559
Abstract
In this report the potential genotoxic and carcinogenic hazards of tetrandrine (518343) were studied using two genetic endpoints, gene mutation and DNA damage. The Salmonella/histidine reversion assay and the SOS/Umu test were used for measuring gene mutations and DNA damage, respectively. The modulating effect of tetrandrine on the genotoxicity of other mutagens and carcinogens was also examined. Tetrandrine was weakly mutagenic to Salmonella-typhimurium (TA-98) (approximately 2.7 times the control) but not with S-typhimurium (TA- 100). Metabolic activation was required for the mutagenic activity. Tetrandrine failed to induce an SOS response at doses up to 150 micrograms and 50 micrograms/treatment with and without metabolic activation, respectively. Tetrandrine produced a dose dependent enhancement of mutations induced by all the mutagens studied. The degree of enhancement ranged from approximately 80 percent with aflatoxin-B1 (1162658) to 200 percent with airborne particles. Tetrandrine increased the 2-aminoanthracene (613138) and trinitrofluorenone (129793) induced SOS responses by more than 300 percent. The authors conclude that tetrandrine was a weak promutagen inducing frameshift mutations and was a potent genotoxic enhancer. The mechanism for the genotoxic enhancement is not understood at present. However, it is suggested that the enhancement may result from an increase in error prone DNA repair.
Keywords
NIOSH-Author; DNA-damage; Nucleic-acids; Genotoxic-effects; Mutagens; Carcinogens; Silicosis; Bioassays; Medical-treatment; Author Keywords: Tetrandrine; Mutagenicity; Ames assay; SOS/Umu test; Salmonella typhimurium
CODEN
MUREAV
CAS No.
518-34-3; 1162-65-8; 613-13-8; 129-79-3
Publication Date
19890301
Document Type
Journal Article
Fiscal Year
1989
NTIS Accession No.
NTIS Price
Issue of Publication
3
ISSN
0027-5107
NIOSH Division
DRDS
Source Name
Mutation Research
State
WV
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