Carcinogenesis, Vol 18, 2429-2433, Copyright © 1997 by Oxford University Press
S Arimoto-Kobayashi, K Kaji, GM Sweetman and H Hayatsu
Previously we reported that when Escherichia coli was treated with N-
nitrosodialkylamine under irradiation with near UV light, mutagenesis of
the bacteria took place: there was no requirement for metabolic activation.
We have now studied the spectra of mutations caused by N-
nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) with UVA
(320-400 nm) irradiation, using standard tester strains for identifying
types of mutations. Induced mutations by NDMA + UVA were the transition
GC-->AT and transversions GC-->CG, GC-->TA and AT-->TA. NDEA +
UVA induced mainly the GC-->CG transversion. In both cases no frameshift
mutations were observed. When O6-alkylguanine-DNA alkyltransferase-
deficient strains of E. coli and Salmonella typhimurium were used, the
mutation levels with both NDMA + UVA and NDEA + UVA became remarkably
higher than those observed with the proficient strains. We measured the
O6-methylguanine (O6-meG) level in calf thymus DNA treated with NDMA + UVA.
The O6-meG level was increased as a function of NDMA concentration and
irradiation time. We also detected N7-methylguanine in DNA treated with
NDMA + UVA. In our previous work we found formation of 8- oxodeoxyguanosine
(8-oxodG) in DNA treated with N-nitrosomorpholine + UVA. The 8-oxodG/dG
ratio in DNA treated with NDMA + UVA increased up to 42-fold over that of
the untreated control and that in DNA treated with NDEA + UVA increased up
to 67-fold. 8-OxodG formation was not affected by replacing H2O in the
reaction mixture with D2O, suggesting that singlet oxygen is not the rate
limiting factor in this photoactivation. We conclude that both alkylation
and oxidation are involved in mutations induced by NDMA + UVA and NDEA +
UVA.
ARTICLES
Mutation and formation of methyl- and hydroxylguanine adducts in DNA caused by N-nitrosodimethylamine and N-nitrosodiethylamine with UVA irradiation
Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Japan.
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