Certain tryptophan photoproducts are inhibitors of cytochrome P450-dependent mutagenicity

Journal Article · Wed Jan 01 00:00:00 EST 1992 · Environmental and Molecular Mutagenesis; (United States)

DOI:https://doi.org/10.1002/em.2850200407· OSTI ID:6387460

Rannug, U; Agurell, E; Cederberg, H ^[1]; Rannug, A ^[2]

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1. Stockholm Univ. (Sweden)
2. National Institute of Occupational Health, Solna (Sweden)

Two photoproducts, derived from UV-irradiation of the amino acid L-tryptophan and with high Ah (TCDD) receptor binding affinity, were tested for genotoxic and antimutagenic effects. The two indolo[3,2-b]carbazole derivatives, with the molecular weights of 284 and 312, respectively, were tested in Saccharomyces cerevisiae strain D7 for mitotic gene conversion and reverse mutation and in strain RS112 for sister chromatid conversion and gene conversion. No significant (P > 0.05) genotoxic effects were found in strain D7, while strain RS112 showed a small but significant increase in the frequency of sister chromatid conversions. In Chinese hamster ovary (CHO) cells the two compounds induced a statistically significant but less than twofold increase in the frequency of sister chromatid exchanges (SCE). No mutations were detected when the compounds were tested in Salmonella tphimurium strains TA98 and TA100. However, both 284 and 312 acted as antimutagens on strain TA100+S9 in the presence of benzo(a)pyrene. The decrease in mutagenicity by the most potent compound 284 was 20 revertants/nmol. This effect could be explained by an inhibitory effect on the cytochrome P450-dependent ethoxyresorufin O-deethylase (EROD) activity as seen in rat hepatocytes. The two compounds were also tested with hamster cells expressing rat cytochrome P-4501A1. The results support the conclusion that this cytochrome P-450 isozyme is inhibited by the tryptophan photoproducts. Similar results were also seen with two other high affinity Ah receptor ligands the quinazolinocarboline alkaloids rutaecapine and dehydrorutaecarpine. 20 refs., 3 figs., 4 tabs.

• OSTI ID: 6387460
• Journal Information: Environmental and Molecular Mutagenesis; (United States), Vol. 20:4; ISSN 0893-6692
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
TRYPTOPHAN
GENETIC RADIATION EFFECTS
CHO CELLS
MUTAGENESIS
MUTAGENS
MUTATIONS
ULTRAVIOLET RADIATION
AMINO ACIDS
ANIMAL CELLS
AROMATICS
AZAARENES
AZOLES
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
CARBOXYLIC ACIDS
ELECTROMAGNETIC RADIATION
GENETIC EFFECTS
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
INDOLES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PYRROLES
RADIATION EFFECTS
RADIATIONS
550400* - Genetics
560120 - Radiation Effects on Biochemicals
Cells
& Tissue Culture