Biomedical subjects

M S Tang

Publications and source records attributed to M S Tang.

At least 37 records · Page 2Linked to original sources

PubMed1994

Purification and properties of beta-fructofuranosidase from Aspergillus oryzae ATCC 76080.

A fructooligosaccharide-producing beta-fructofuranosidase was purified from the crude extract of Aspergillus oryzae ATCC 76080 through successive steps of ultrafiltration, DEAE-Sepharose CL-6B ion-exchange chromatography, preparative isoelectric focusing electrophoresis and Sephacryl S-200 gel filtration. The purified enzyme had an optimal pH of 5-6, an optimal temperature of 50 degrees C, a Km value of 0.53 M for catalyzing selftransfer reaction from sucrose. The molecular weight was 87 kDa by gel filtration. Mercuric ion (0.25 mM), p-hydroxymercuribenzoate (0.25 mM) and N-bromosuccinimide (0.5 mM), significantly inhibited the enzyme activity. The enzyme showed both transfructosylation and hydrolytic action in 0.5 to 50% sucrose. The transfructosylation ratio increased as the sucrose concentration increased and it was 88.5% at 50% sucrose. The main fructooligosaccharides produced from sucrose were 1-kestose and nystose.

Aspergillus oryzae↗

PubMed1993

Comparison of sequence preference of tomaymycin- and anthramycin-DNA bonding by exonuclease III and lambda exonuclease digestion and UvrABC nuclease incision analysis.

The DNA bonding sites of two pyrrolo[1,4]benzodiazepine derivatives--tomaymycin (Tma) and anthramycin (Atm)--were identified by exonuclease III (exo III) digestion, lambda exonuclease (lambda exo) digestion, and UvrABC nuclease incision analysis. exo III digestion stalls 4-5 bases 3' to a drug-DNA adduct. While this method can recognize most of the Atm-and Tma-DNA modification sites, it is complicated in that exo III digestion is also stalled by certain unmodified sequences and by drug bound to the opposite strand. lambda exo digestion stalls 1-2 bases 5' to a drug-DNA adduct. The lambda exo method also recognizes most of the drug-DNA bonding sites and renders a cleaner background; however, it is also affected by opposite-strand drug bonding. Due to their intrinsic digestion polarities, these two exonucleases tend to be stalled by the drug-DNA adduct at one end of the DNA molecule. Purified UvrA, UvrB, and UvrC proteins acting together make dual incisions 6-8 bases 5' and 4 bases 3' to a Atm- or Tma-DNA adduct. This nuclease complex recognizes all the Tma- and Atm-DNA bonding sites identified by exonuclease digestion methods, and all the UvrABC incisions can be attributed to drug modifications in the incised DNA strand. The degree of UvrABC nuclease incision increases with increasing drug concentrations for DNA modification. Using the UvrABC incision method, we have identified the sequence preference of Tma- and Atm-DNA adduct formation in three DNA fragments, and we have found that these two drugs have different preferred sites for adduction. Both Tma- and Atm-DNA bonding is strongly influenced by the 5' and 3' neighboring bases; the orders of preferred 5' and 3' bases for Tma are A > G, T > C, and A, C > G, T, and for Atm the orders are A > G > T > C and A > G > T, C. The preferred triplets for Tma bonding are -AGA- > -GGC-, -TGC-, and AGC- and for Atm are -AGA-, -AGG- > -GGA-, -GGG-.

Anthramycin↗

PubMed1993

Nucleotide excision repair.

Nucleotide excision repair is the major DNA repair mechanism in all species tested. This repair system is the sole mechanism for removing bulky adducts from DNA, but it repairs essentially all DNA lesions, and thus, in addition to its main function, it plays a back-up role for other repair systems. In both pro- and eukaryotes nucleotide excision is accomplished by a multisubunit ATP-dependent nuclease. The excision nuclease of prokaryotes incises the eighth phosphodiester bond 5' and the fourth or fifth phosphodiester bond 3' to the modified nucleotide and thus excises a 12-13-mer. The excision nuclease of eukaryotes incises the 22nd, 23rd, or 24th phosphodiester bond 5' and the fifth phosphodiester bond 3' to the lesion and thus removes the adduct in a 27-29-mer. A transcription repair coupling factor encoded by the mfd gene in Escherichia coli and the ERCC6 gene in humans directs the excision nuclease to RNA polymerase stalled at a lesion in the transcribed strand and thus ensures preferential repair of this strand compared to the nontranscribed strand.

Animals↗

PubMed1992

A comparison of the rates of reaction and function of UVRB in UVRABC- and UVRAB-mediated anthramycin-N2-guanine-DNA repair.

The repair of anthramycin-DNA adducts by the UVR proteins in Escherichia coli follows two pathways: the adducts may be incised by the combined actions of UVRA, UVRB, and UVRC, or alternatively, the anthramycin may be removed by UVRA and UVRB in the absence of UVRC and with no DNA strand incision. To assess the competition between these two competing pathways, the rate of UVRABC-mediated excision repair of anthramycin-N2-guanine DNA adducts and the rate of UVRAB-mediated removal of the adduct were measured with single end-labeled DNAs under identical reaction conditions. UVR protein concentrations of 15 nM UVRA, 100 nM UVRB, and 10 nM UVRC protein were chosen to mimic in vivo concentrations. With these UVR protein concentrations and anthramycin-DNA concentrations of 1-2 nM the incision reaction and the release reactions are described by first-order kinetics. The rate of the UVRABC reaction, measured as the increase in incised fragments, was six to seven times faster than the rate of the UVRAB reaction, measured as the decrease in incised fragments. The UVRABC incision rate on anthramycin-modified linear DNA was four to five times the incision rate measured on the same DNA irradiated with ultraviolet light. We also investigated the role of the ATPase function of UVRB in UVRAB-mediated anthramycin removal. We found that a UVRB analogue with alanine at arginine 51, which retains near wild type ATPase activity, supported removal of anthramycin in the presence of UVRA, whereas a UVRB analogue with alanine at lysine 45, which abolishes the ATPase activity, did not. UVRB*, a specific proteolytic cleavage product of UVRB which retains the ATPase activity, did support removal of anthramycin in the presence of UVRA.

Anthramycin↗

PubMed1992

Differences and similarities in the repair of two benzo[a]pyrene diol epoxide isomers induced DNA adducts by uvrA, uvrB, and uvrC gene products.

We have determined the role of the uvrA, uvrB, and uvrC genes in Escherichia coli cells in repairing DNA damage induced by three benzo[a]pyrene diol epoxide isomers. Using the phi X174 RF DNA-E. coli transfection system, we have found that BPDE-I or BPDE-II modified phi X174 RF DNA has much lower transfectivity in uvrA, uvrB, and uvrC mutant cells compared to wild type cells. In contrast, BPDE-III modification of phi X174 RF DNA causes much less difference in transfectivity between wild type and uvr- mutant cells. Moreover, BPDE-I and -II-DNA adducts are much more genotoxic than are BPDE-III-DNA adducts. Using purified UVRA, UVRB, and UVRC proteins, we have found that these three gene products, working together, incise both BPDE-I- and BPDE-III-DNA adducts quantitatively and, more importantly, at the same rate. In general, UVRABC nuclease incises on both the 5' (six to seven nucleotides) and 3' (four nucleotides) sides of BPDE-DNA adducts with similar efficiency with few exceptions. Quantitation of the UVRABC incision bands indicates that both of these BPDE isomers have different sequence selectivities in DNA binding. These results suggest that although UVR proteins can efficiently repair both BPDE-I- and BPDE-III-DNA adducts, in vivo the uvr system is the major excision mechanism for repairing BPDE-I-DNA adducts but may play a lesser role in repairing BPDE-III-DNA adducts. It is possible the low lethality of BPDE-III-DNA adducts is due to less complete blockage of DNA replication.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗

PubMed1991

Repair of helix-stabilizing anthramycin-N2 guanine DNA adducts by UVRA and UVRB proteins.

The transfectivity of anthramycin (Atm)-modified phi X174 replicative form (RF) DNA in Escherichia coli is lower in uvrA and uvrB mutant cells but much higher in uvrC mutant cells compared to wild-type cells. Pretreatment of the Atm-modified phage DNA with purified UVRA and UVRB significantly increases the transfectivity of the DNA in uvrA or uvrB mutant cells. This pretreatment greatly reduces the UVRABC nuclease-sensitive sites (UNSS) and Atm-induced absorbance at 343 nm in the Atm-modified DNA without producing apurinic sites. The reduction of UNSS is proportional to the concentrations of UVRA and UVRB and the enzyme-DNA incubation time and requires ATP. We conclude that there are two different mechanisms for repairing Atm-N2 guanine adducts by UVR proteins: (1) UVRA and UVRB bind to the Atm-N2 guanine double-stranded DNA region and consequently release the Atm from the adducted guanine; (2) UVRABC makes an incision at both sides of the Atm-DNA adduct. The latter mechanism produces potentially lethal double-strand DNA breaks in Atm-modified phi X174 RF DNA in vitro.

Adenosine Triphosphatases↗

PubMed1991

Suppression of cyclobutane and mean value of 6-4 dipyrimidines formation in triple-stranded H-DNA.

We have determined the effect of H-DNA formation on the distributions of two ultraviolet (UV) light induced photoproducts--cyclobutane dipyrimidines and mean value of 6-4 dipyrimidines. A region of DNA containing the sequence (dT-dC)18.(dA-dG)18 was treated under conditions that specifically yield the triple-stranded H-y3 or H-y5 DNA structure and then irradiated with UV. The positions of cyclobutane dipyrimidines and mean value of 6-4 dipyrimidines were determined by T4 endonuclease V cleavage and by hot piperidine cleavage, respectively. Formation of H-DNA structures greatly decreased the photoproduct yield in the (dT-dC)18.(dA-dG)18 region but not elsewhere in the DNA. Suppression of photoproduct formation is greater in half of the repeat, reflecting whether the DNA is in the H-y3 or H-y5 conformation. Within the repeat, the suppression was less in the middle and toward the ends. Models for the suppression of photoproduct formation in H-DNA and the possible utility of our findings are discussed.

Base Composition↗

PubMed1989

Quantification of aminofluorene adduct formation and repair in defined DNA sequences in mammalian cells using the UVRABC nuclease.

Using the UVRABC nuclease as a reagent coupled with DNA restriction and hybridization analysis we have developed a method to quantify N-acetoxy-2-acetylaminofluorene (NAAAF)-induced DNA damage in the coding and noncoding sequences of the dihydrofolate reductase (DHFR) gene in Chinese hamster ovary (CHO) cells. High performance liquid chromatography analysis shows that the only DNA adduct formed in NAAAF-treated CHO cells is N-(deoxyguanosine-C8-yl)-2-aminofluorene (dG-C8-AF). DNA sequencing analysis demonstrates that the UVRABC nuclease incises at all potential sites in which dG-C8-AF adduct may form in linear DNA fragments. We have found that the formation and removal of dG-C8-AF adducts in the coding and 3' downstream noncoding sequences of the DHFR domain are similar in cells treated with 10 microM NAAAF (3.1 adducts/14 kilobases); DNA adduct removal attains 70% for both sequences within 24 h. This result contrasts with that obtained for the repair of cyclobutane dipyrimidines in the DHFR gene, in which the repair efficiency is much higher in the coding region than in the 3' downstream noncoding region. Our results suggest that in CHO cells the repair pathway for aminofluorene DNA adducts is not the same as that for cyclobutane dipyrimidines. This new technique has the potential to detect a variety of chemical carcinogen induced DNA adducts at the gene level in cultured cells and in DNA isolated from animal tissues.

2-Acetylaminofluorene↗

PubMed1989

Recognition and repair of 2-aminofluorene- and 2-(acetylamino)fluorene-DNA adducts by UVRABC nuclease.

Recognition of damage induced by N-hydroxy-2-aminofluorene (N-OH-AF) and N-acetoxy-2-(acetylamino)fluorene (NAAAF) in both phi X174 RFI supercoiled DNA and a linear DNA fragment by purified UVRA, UVRB, and UVRC proteins was investigated. We have previously demonstrated that N-OH-AF and NAAAF treatments produce N-(deoxyguanosin-8-yl)-2-aminofluorene (dG-C8-AF) and N-(deoxyguanosin-8-yl)-2-(acetylamino)fluorene (dG-C8-AAF), respectively, in DNA. Using a piperidine cleavage method and DNA sequence analysis, we have found that all guanine residues can be modified by N-OH-AF and NAAAF. These two kinds of adducts have different impacts on the DNA helix structure; while dG-C8-AF maintains the anti configuration, dG-C8-AAF is in the syn form. phi X174 RF DNA-Escherichia coli transfection results indicate that while the uvrA, uvrB, and uvrC gene products are needed to repair dG-C8-AAF, the uvrC, but not the uvrA or uvrB gene products, is needed for repair of dG-C8-AF. However, we have found that in vitro the UVRA, UVRB, and UVRC proteins must work in concert to nick both dG-C8-AF and dG-C8-AAF. In general, the reactions of UVRABC nuclease toward dG-C8-AF are similar to those toward dG-C8-AAF; it incises seven to eight nucleotides from the 5' side and three to four nucleotides from the 3' side of the DNA adduct. Evidence is presented to suggest that hydrolysis on the 3' and 5' sides of the damaged base by UVRABC nuclease is not simultaneous and that at least occasionally hydrolysis occurs only on the 3' side or on the 5' side of the damage site. The possible mechanisms of UVRABC nuclease incision for AF-DNA are discussed.

2-Acetylaminofluorene↗

PubMed1988

Recognition of the DNA helix stabilizing anthramycin-N2 guanine adduct by UVRABC nuclease.

The binding of the anti-tumor antibiotic anthramycin to a defined linear DNA fragment was investigated using both exonuclease III and lambda exonuclease. We show that most of the guanine residues are reactive toward anthramycin; however, several guanine residues showed preferential reactivity for the drug. Using purified UVRA, UVRB and UVRC proteins we present evidence that these three proteins in concert are able to recognize and produce specific strand cleavage flanking anthramycin-DNA adducts. The cleavage of anthramycin adducts by UVRABC nuclease is specific and results in strand breaks at five or six bases 5' and three or four bases 3'-flanking an adduct. At some guanine residues single incisions were observed only on one side of the adduct. The 5' strand breaks observed often occurred as doublet bands on sequencing gels, indicating plasticity in the site of 5' cleavage whereas the 3' cleavage did not show this effect. When DNA fragments modified with elevated levels of anthramycin were used as substrates the activity of the UVRABC nuclease toward the anthramycin adducts decreased. Possible mechanisms for the recognition and specific cleavage of the helix-stabilizing anthramycin DNA adduct and other helix destabilizing lesions by the UVRABC nuclease are discussed.

Anthramycin↗

PubMed1988

Recognition and repair of the CC-1065-(N3-adenine)-DNA adduct by the UVRABC nucleases.

The recognition and repair of the helix-stabilizing and relatively nondistortive CC-1065-(N3-adenine)-DNA adduct by UVRABC nuclease has been investigated both in vivo with phi X174 RFI DNA by a transfection assay and in vitro by a site-directed adduct in a 117 base pair fragment from M13mp1. CC-1065 is a potent antitumor antibiotic produced by Streptomyces zelensis which binds within the minor groove of DNA through N3 of adenine. In contrast to the helix-destabilizing and distortive modifications of DNA caused by ultraviolet light or N-acetoxy-2-(acetylamino)fluorene, CC-1065 increases the melting point of DNA and decreases the S1 nuclease activity. Using a viral DNA-Escherichia coli transfection system, we have found that the uvrA, uvrB, and uvrC genes, which code for the major excision repair proteins for UV- and NAAAF-induced DNA damage, are also involved in the repair of CC-1065-DNA adducts. In contrast, the uvrD gene product, which has been found to be involved in the repair of UV damage, has no effect in repairing CC-1065-DNA adducts. Purified UVRA, UVRB, and UVRC proteins must work in concert to incise the drug-modified phi X174 RFI DNA. Using a site-directed and multiple CC-1065 modified (MspI-BstNI) 117 base pair fragment from M13mp1, we have found that UVRABC nuclease incises at the eighth phosphodiester bond on the 5' side of the CC-1065-DNA adduct on the drug-modified strand.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine↗

PubMed1988

Mutational spectrum and recombinogenic effects induced by aminofluorene adducts in bacteriophage M13.

Double-stranded replicative form (RFI) DNA of bacteriophage M13 strain M13mp10 which carries partial lacZ gene has been modified in vitro to various extents with N-hydroxy-2-amino-fluorene (N-OH-AF) and then transfected into E. coli cells. High-performance liquid chromatography (HPLC) analysis results demonstrate that the sole adduct (95%) formed in modified DNA is N-(deoxyguanosine-8-yl)-2-aminofluorene (dG-C8-AF). Approximately 20 adducts per RFI molecule constitute 1 lethal event when plaque-forming ability is assayed on E. coli cells which have received no prior SOS induction. The mutagenicity of dG-C8-AF adducts was assayed by measuring loss of beta-galactosidase activity as a function of adducts per molecule. A dose-dependent increase in Lac- mutants was observed, with a 4-fold increase in mutants per survivor at 30 adducts/molecule. The mutations produced, characterized by DNA sequencing, occur predominantly at either G or C positions different from those observed in the spontaneous mutant spectrum. Restriction-mapping results show that in our assay system, dG-C8-AF adducts induce a previously unreported recombinogenic activity.

Bacteriophages↗

PubMed1988

Processing of 2-aminofluorene and 2-acetylaminofluorene DNA adducts in Chinese hamster ovary cells.

The effects of 2-aminofluorene (AF) DNA damage on cytotoxicity and DNA-mediated genetic transformation were investigated in Chinese hamster ovary (CHO) cells. N-Acetoxy-2-acetylaminofluorene (NA-AAF) treatment of DNA repair-proficient AT3-2 cells and UVL-10, a UV-hypersensitive mutant cell line derived from AT3-2, showed that UVL-10 cells were markedly more sensitive than AT3-2 cells to NA-AAF cytotoxicity. Analysis of cellular DNA from NA-AAF-treated cell cultures showed that AF was the predominant DNA adduct formed in both cell lines, while formation of 2-acetylaminofluorene (AAF) DNA adducts was not detected in cellular DNA samples of either cell line. Analysis of AF adduct removal showed that kinetics and extent of AF removal were similar in both cell lines. The effects of cellular processing of AAF DNA adducts in CHO cells were examined by introducing plasmid pSV2gpt DNA containing AAF damage into AT3-2 and UVL-10 cell lines by transfection. For comparative purposes, AF-containing pSV2gpt was also used in parallel experiments. In transfection experiments with AAF-containing pSV2gpt DNA, yields of gpt+ transformants declined relative to control frequencies in a much more pronounced manner in repair-deficient UVL-10 cells than in repair-proficient AT3-2 cells. In contrast, transfection with pSV2gpt DNA containing AF adducts had no apparent effect on transformation frequencies in either cell line, even at very high levels of modification. Results of co-transformation experiments in which transfected AAF-containing pSV2gpt DNA molecules were not subjected to selection for phenotype showed that in repair-deficient UVL-10 cells, AAF damage in pSV2gpt apparently interfered with the ultimate association of transfected DNA with recipient cell DNA.

2-Acetylaminofluorene↗

PubMed1986

The relative cytotoxicity and mutagenicity of cyclobutane pyrimidine dimers and (6-4) photoproducts in Escherichia coli cells.

In order to calculate the relative cytotoxicity and mutagenicity of (5-6) cyclobutane pyrimidine dimers and (6-4) photoproducts, we have measured survival and mutation induction in UV-irradiated excision-deficient E. coli uvrA cells, with or without complete photoreactivation of the (5-6) dimers. Radioimmunoassays with specificity for (5-6) dimers or (6-4) photoproducts have shown that maximum photoreactivation eliminates all of the (5-6) dimers produced up to 10 Jm-2 254-nm light, while it has no effect on (6-4) photoproducts. These results were confirmed by measuring the frequency of T4 endonuclease V-sensitive sites. Based on the best fit equations for survival and mutation induction, we have found that the calculated cytotoxicity of (6-4) photoproducts is similar to that of (5-6) dimers; however, the former is much more mutagenic than the latter.

Dose-Response Relationship, Radiation↗

PubMed1985

Repair of psoralen and acetylaminofluorene DNA adducts by ABC excinuclease.

Escherichia coli UvrA, UvrB and UvrC proteins acting in concert remove the major ultraviolet light-induced photoproduct, the pyrimidine dimer, from DNA in the form of a 12 to 13-nucleotide long single-stranded fragment. In vivo data indicate that the UvrABC enzyme is also capable of removing other nucleotide diadducts as well as certain nucleotide monoadducts from DNA and initiating the repair process that leads to removal of interstrand crosslinks caused by some bifunctional chemical agents. We have determined the action mechanism of the enzyme on nucleotide monoadducts produced by 4'-hydroxymethyl-4,5',8-trimethylpsoralen and N-acetoxy-N-2-acetylaminofluorene. In both cases we find that the enzyme hydrolyzes the eighth phosphodiester bond 5' and the fifth phosphodiester bond 3' to the modified base. This cutting pattern is similar to that observed with diadduct substrate, the only difference being that while the enzyme incises the fourth or fifth phosphodiester bond 3' to the pyrimidine dimer it always hydrolyzes the fifth bond relative to monoadducts. Our results also suggest that ABC excinuclease cuts the same two phosphodiester bonds on both sides of a T whether that T has a psoralen monoadduct or is involved in psoralen-mediated interstrand crosslink.

2-Acetylaminofluorene↗

PubMed1985

Differentiation of apurinic/apyrimidinic sites and single-strand breaks in DNA by formamide- and alkaline-sucrose gradient sedimentation.

The excision repair of DNA damaged by physical or chemical agents may produce either apurinic/apyrimidinic (AP) sites or single-strand breaks (SSB) in the DNA. Alkaline-sucrose gradient sedimentation and alkaline elution, techniques generally used for the study of DNA repair which depend upon high pH to denature the DNA, cannot differentiate between these possibilities. A simple method for the quantitative measurement of SSB in DNA which leaves any AP sites intact is presented. This method relies upon the separation by size of the fragments resulting from the denaturation of the DNA under neutral conditions by sedimentation through gradients of sucrose in formamide. By combining the use of both formamide- and alkaline-sucrose sedimentation methods, we can quantify both AP sites and SSB in DNA.

Apurinic Acid↗

PubMed1985

Single-strand breakage of DNA in UV-irradiated uvrA, uvrB, and uvrC mutants of Escherichia coli.

We transduced the uvrA6, uvrB5, uvrC34, and uvrC56 markers from the original mutagenized strains into an HF4714 background. Although in the original mutagenized strains uvrA6 cells are more UV sensitive than uvrB5 and uvrC34 cells, in the new background no significant difference in UV sensitivity is observed among uvrA6, uvrB5, and uvrC34 cells. No DNA single-strand breaks are detected in UV-irradiated uvrA6 or uvrB5 cells, whereas in contrast a significant number of single-strand breaks are detected in both UV-irradiated uvrC34 and uvrC56 cells. The number of single-strand breaks in these cells reaches a plateau at 20-J/m2 irradiation. Since these single-strand breaks can be detected by both alkaline sucrose and neutral formamide-sucrose gradient sedimentation, we concluded that the single-strand breaks observed in UV-irradiated uvrC cells are due to phosphodiester bond interruptions in DNA and are not due to apurinic/apyrimidinic sites.

Centrifugation, Density Gradient↗

PubMed1985

Interactions of benzo(a)pyrene diol-epoxides with linear and supercoiled DNA.

Previous spectroscopic studies of the major adduct formed by reaction of (+/-)-7r,8t-dihydroxy-9t, 10t-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BPDE-I) with linear DNA have been interpreted to suggest that the adduct is not intercalated in the double helix. However, studies of the electrophoretic mobility of supercoiled DNA treated with BPDE-I suggest that the adduct is intercalated. To resolve these interpretations, we have studied the reaction of BPDE-I with supercoiled and linear DNA. The kinetics of DNA-catalyzed hydrolysis and of covalent binding are similar for the two DNAs; supercoiled DNA exhibits a 20% increase in the rate of hydrolysis of BPDE-I at low DNA concentration compared to linear DNA. Fluorescence excitation spectra and fluorescence quenching experiments provide no support for a model in which BPDE-I adducts are intercalated in supercoiled DNA. When deoxyribonucleoside adducts were analyzed by high-performance liquid chromatography, identical distributions of BPDE-I adducts were found for supercoiled and linear DNA. These data are consistent with a previously proposed model (Hogan, M. E., Dattagupta, N., and Whitlock, J.P., Jr. J. Biol. Chem., 256: 4504-4513, 1981; Taylor, E.R., Miller, K. J., and Bleyer, A. J. J. Biomol. Struct. Dyn., 1: 883-904, 1983), in which the major BPDE-I adduct in both linear and supercoiled DNA exists in a conformation which allows stacking with the neighboring base pair and introduces a "kink" into the path of the helical axis. Although this model provides an explanation for all available experimental data, there are undoubtedly other DNA adduct conformational models which are also consistent with the data.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗