Selective covalent binding of the active sulfate ester of the carcinogen 5-(hydroxymethyl)chrysene to the adenine residue of calf thymus DNA

Journal Article · · Chem. Res. Toxicol.; (United States)

DOI:https://doi.org/10.1021/tx00007a003· OSTI ID:6202160

Okuda, H; Nojima, H; Miwa, K; Watanabe, N; Watabe, T

5-(Hydroxymethyl)chrysene (5-HCR) sulfate, an active metabolite of the carcinogen 5-HCR, bound significantly in a covalent manner to the purine bases of calf thymus DNA through its 5-methylene carbon with loss of a sulfate anion when incubated at pH 7.4 and 37/degrees/C. From the DNA were isolated two purine base adducts by high-pressure liquid chromatography, and they were identified as N/sup 6/-((chrysen-5-yl)methyl)adenine and N/sup 2/((chrysen-5-yl)methyl)guanine with the corresponding synthetic specimens. The purine base adducts, appearing in the ratio 1 to 27 for guanine to adenine in the chromatogram, accounted for about 60% of the total covalent binding of 5-HCR sulfate to the DNA. 5-HCR sulfate also reacted specifically with the exocyclic amino groups of the purine bases of 2'-deoxyadenosine 5'-phosphate and 2'-deoxyguanosine 5'-phosphate at much lower rates than did with those of calf thymus DNA. Denaturing the DNA by heating followed by rapid cooling, covalent binding of 5-HCR sulfate to it markedly decreased with the increasing ratio of N/sup 2/-guanine to N/sup 6/-adenine adducts (1:3:6). These results strongly suggest that secondary structure of DNA has an influence on the covalent binding of 5-HCR sulfate and that intercalation of the sulfate ester into DNA base pairs plays an important role in its preferential binding to N/sup 6/ of the adenine residue of native DNA.

• Research Organization: Tokyo College of Pharmacy (Japan)
• OSTI ID: 6202160
• Journal Information: Chem. Res. Toxicol.; (United States), Journal Name: Chem. Res. Toxicol.; (United States) Vol. 2:1; ISSN CRTOE
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
ADENINES
AMINES
ANIMALS
ANTIMETABOLITES
AROMATICS
AZAARENES
BIOSYNTHESIS
BODY
CALVES
CATTLE
CHROMATOGRAPHY
CHRYSENE
CONDENSED AROMATICS
DNA
DNA ADDUCTS
DOMESTIC ANIMALS
DRUGS
ESTERS
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
LIQUID COLUMN CHROMATOGRAPHY
LYMPHATIC SYSTEM
MAMMALS
METABOLIC ACTIVATION
METABOLITES
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
OXYGEN COMPOUNDS
PURINES
RUMINANTS
SEPARATION PROCESSES
SULFATES
SULFUR COMPOUNDS
SYNTHESIS
THYMUS
VERTEBRATES