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A K Basu

Publications and source records attributed to A K Basu.

At least 181 records · Page 10Linked to original sources
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Identification of adducts formed by reaction of guanine nucleosides with malondialdehyde and structurally related aldehydes.

Malondialdehyde and a series of acrolein derivatives substituted in the beta-position with good leaving groups react with guanine and guanine nucleosides to form two different types of adducts. The reaction with guanosine is typical. One adduct exhibits ultraviolet absorbance maxima at 253, 319, and 348 nm and is fluorescent. Its NMR spectrum exhibits three new aromatic proton resonances derived from malondialdehyde. The mass spectrum exhibits an M + 1 at 320. The spectroscopic properties are consistent with the structure, 3-beta-D-erythro-pentofuranosyl-pyrimido[1,2-alpha]purin-10(3H)-one (PyP-ribose). The second guanosine adduct is an equal mixture of diastereomers that exhibit ultraviolet maxima at 217 and 244 nm and mirror image circular dichroism spectra. The NMR spectrum and mass spectrum (M + 1 = 392) indicate the addition of two molecules of MDA to one molecule of guanosine. Two-dimensional NMR (COSY) analysis reveals the presence of propano and enal functionalities. The spectroscopic and chemical properties suggest an oxadiazabicyclo[3.3.1]nonene structure that is confirmed by X-ray crystallography. Comparison of the deoxyguanosine adducts of malondialdehyde to those of the structurally related carbonyl compounds, methyl glyoxal and acrolein, provides a structural basis to explain the unique ability of malondialdehyde to induce frameshift mutations in bacterial mutagenesis systems.

Acrolein↗
PubMedDate not supplied

Reductive metabolism of 1-nitropyrene accompanies deamination of cytosine.

1-Nitropyrene (1-NP), a common environmental pollutant, is a mutagen and tumorigen. Nitroreduction is a major pathway by which 1-NP is metabolized. In order to study the mutational specificity of reductively activated 1-NP, single-stranded M13mp18 DNA was treated with tritium-labeled 1-nitrosopyrene in the presence of ascorbic acid to generate N-hydroxy-1-aminopyrene in situ. HPLC analysis of the treated DNA, following enzymatic digestion, showed that > 95% of tritium was located in one major adduct, N-(deoxyguanosin-8-yl)-1-aminopyrene. Transfection of these adducted M13 DNA in Escherichia coli indicated a dose-dependent reduction in viability with concomitant enhancement in mutagenesis in the lacZ gene fragment. Without SOS functions, the major type of mutation was C-->T transition (48%). Further studies have shown that cytosine deamination occurred during ascorbic acid-induced nitroreduction, which was likely responsible for the C-->T transitions. Deamination of cytosine alco occurred at a significant frequency when nitroreduction of either 1-NP or 1-nitrosopyrene was catalyzed by xanthine oxidase, a mammalian nitroreductase.

Base Sequence↗