Biomaterial Database

Studies on the binding and transcriptional properties of aflatoxin B1-8,9-epoxide. 1994

F L Yu, and W Bender, and A Hutchcroft

Department of Biomedical Sciences, University of Illinois, College of Medicine at Rockford 61107.

[3H]Aflatoxin B1-8,9-epoxide ([3H]AFB1-8,9-epoxide), the putative ultimate carcinogen of AFB1, was synthesized and tested for its binding specificity to and transcriptional effect on several single- and double-stranded DNAs containing cytosine. The test was carried out over a 200-fold concentration range (i.e. 0.1-20 microgram [3H]AFB1-8,9-epoxide per 0.025 A260 units of DNA). The results show: (i) [3H]AFB1-8,9-epoxide bound preferentially to the double-stranded alternating co-polymer poly[d(G-C)] over the double-stranded poly(dG).poly(dC) and single-stranded poly(dG) or poly(dC) homopolymers. (ii) The binding affinity of [3H]AFB1-8,9-epoxide to poly(dC) was essentially the same as the poly(dG). (iii) Under identical conditions, [3H]AFB1-8,9-epoxide bound to poly(dG).poly(dC) 2.5-3 times more than to poly[d(I-C)]; however, poly[d(I-C)]-directed RNA synthesis was clearly more sensitive to [3H]AFB1-8,9-epoxide inhibition than poly(dG).poly(dC). Conversely, the binding affinity of [3H]AFB1-8,9-epoxide to poly(dC) and to poly[d(I-C)] was quite similar, yet poly(dC)-directed RNA synthesis was much more resistant to [3H]AFB1-8,9-epoxide inhibition than poly[d(I-C)]. (iv) After [3H]AFB1-8,9-epoxide was hydrolyzed to [3H]AFB1-8,9-dihydrodiol (0.01 N NaOH, 10 min 23 degrees C), it was no longer able to bind poly[d(G-C)] or to inhibit poly[d(G-C)]-directed RNA synthesis. These results confirm our earlier studies using microsome-activated AFB1 and AFB1-Cl2 that AFB1 after activation is able to bind cytosine in DNA, and the binding is not via AFB1-8,9-dihydrodiol. Furthermore, the results also suggest that AFB1 adducts may not have the same biological effect depending on the base, sequence as well as the conformation of the DNA where the adducts are formed.

UI	MeSH Term	Description	Entries
D011066	Poly C	A group of cytosine ribonucleotides in which the phosphate residues of each cytosine ribonucleotide act as bridges in forming diester linkages between the ribose moieties.	Cytosine Polynucleotides,Polycytidylic Acid,Polycytidylic Acids,Acid, Polycytidylic,Acids, Polycytidylic,Polynucleotides, Cytosine
D011068	Poly G	A group of guanine ribonucleotides in which the phosphate residues of each guanine ribonucleotide act as bridges in forming diester linkages between the ribose moieties.	Guanine Polynucleotides,Polyguanylic Acids,Acids, Polyguanylic,Polynucleotides, Guanine
D004247	DNA	A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).	DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D012313	RNA	A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)	RNA, Non-Polyadenylated,Ribonucleic Acid,Gene Products, RNA,Non-Polyadenylated RNA,Acid, Ribonucleic,Non Polyadenylated RNA,RNA Gene Products,RNA, Non Polyadenylated
D014158	Transcription, Genetic	The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.	Genetic Transcription
D016604	Aflatoxin B1	A potent hepatotoxic and hepatocarcinogenic mycotoxin produced by the Aspergillus flavus group of fungi. It is also mutagenic, teratogenic, and causes immunosuppression in animals. It is found as a contaminant in peanuts, cottonseed meal, corn, and other grains. The mycotoxin requires epoxidation to aflatoxin B1 2,3-oxide for activation. Microsomal monooxygenases biotransform the toxin to the less toxic metabolites aflatoxin M1 and Q1.	Aflatoxin B(1),Aflatoxin B,Aflatoxin B1 Dihydrochloride, (6aR-cis)-Isomer,Aflatoxin B1, (6aR-cis)-Isomer, 14C-Labeled,Aflatoxin B1, (6aR-cis)-Isomer, 2H-Labeled,Aflatoxin B1, (6aR-cis)-Isomer, 3H-Labeled,Aflatoxin B1, cis(+,-)-Isomer,HSDB-3453,NSC-529592,HSDB 3453,HSDB3453,NSC 529592,NSC529592