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PubMed2004

Differential susceptibility to chromatid breaks induced by bleomycin in sub-fertile and fertile bovines.

The rate of chromatid breaks was studied in cows with a history of sub-fertility by means of a test based on measurement of the average of breaks induced in lymphocytes of peripheral blood cultures. Fourteen female specimens were divided into two groups: fertile and sub-fertile. Peripheral blood lymphocytes were cultured and prepared for cytogenetic analysis. Two types of culture were established for each animal to evaluate the response of peripheral blood lymphocyte cultures to the genotoxic effects of bleomycin. The first culture did not receive bleomycin treatment (spontaneous chromosome aberrations). Our results showed that median breaks per cell (b/c) (+/-semirange) for spontaneous culture of the fertile and sub-fertile animals and bleomycin sensitivity assay for fertile and sub-fertile animals were 0.00+/-0.06, 0.02+/-0.03, 0.08+/-0.05 and 0.22+/-0.09, respectively. There was no significant difference (P>0.05) in the chromosomal breakage in lymphocytes not exposed to bleomycin; however, in comparing the number of chromatid breaks per cell in cultures treated with bleomycin, the sub-fertile group showed a significantly higher (P<0.05) level than the fertile group. These findings have implications both for identifying cattle with less than optimum fertility as well as for providing potential avenues to study the origins of sub-fertility.

Animals↗
PubMed2004

Distinct functions for WRN and TP53 in a shared pathway of cellular response to 1-beta-D-arabinofuranosylcytosine and bleomycin.

Mutations in the WRN or the TP53 genes lead to spontaneous genetic instability, an elevated risk of tumor formation, and sensitivity to compounds that interfere with DNA replication, such as camptothecin and DNA interstrand cross-linking drugs. We investigated the hypothesis that WRN and TP53 are involved in cellular responses to DNA replication-blocking lesions by exposing WRN deficient and TP53 mutant lymphoblastoid cell lines (LCLs) to 1-beta-d-arabinofuranosylcytosine (AraC) and bleomycin. Loss of WRN or TP53 function resulted in induction of apoptosis and lesser proliferative survival in response to AraC and bleomycin. WRN and TP53 operate in a shared DNA damage response pathway, since in cells in which TP53 was inactivated by SV-40 transformation, no difference in AraC and bleomycin sensitivity was found regardless of WRN status. In contrast to TP53 mutant LCLs, WRN-deficient cells showed unaffected cell cycle arrest after AraC and bleomycin exposure, which indicates that WRN is not involved in DNA damage-activated cell cycle arrest. Neither WRN nor TP53 deficiency affected cellular recovery from exposure to AraC and bleomycin, which disagrees with a direct role in repair of these DNA lesions. Our results indicate that WRN and TP53 perform different functions in a shared DNA damage response pathway.

Antimetabolites, Antineoplastic↗
PubMed2003

Electrochemo-gene therapy of cancer: intratumoral delivery of interleukin-12 gene and bleomycin synergistically induced therapeutic immunity and suppressed subcutaneous and metastatic melanomas in mice.

To treat established melanoma in mice, intratumoral transfer of bleomycin and/or an interleukin (IL)-12 expression vector was performed by means of electroporation. Although either bleomycin alone or the IL12 gene alone significantly suppressed the subcutaneous tumors, the combination therapy drastically improved the therapeutic outcome. Three of eight mice (37.5%) that received both bleomycin and the IL12 gene showed complete remission of the preestablished tumors and rejected subsequent rechallenge with the tumor cells. We also examined whether electrochemo-gene therapy for subcutaneous tumor mass induced suppression of pulmonary metastasis that had been established by intravenous inoculation of the melanoma cells. Although metastatic foci were significantly reduced in number in groups that were given IL12 gene alone or bleomycin plus IL12 gene, it was only the combination therapy that significantly prolonged the mean survival period of the tumor-bearing animals. Natural killer (NK) and cytotoxic T lymphocyte cytolytic activities were markedly enhanced in the mice that received the chemo-gene therapy, while IL12 gene therapy alone partially elevated the NK cytotoxicity. The present study suggests that the electroporation-mediated delivery of the IL12 gene and bleomycin synergistically elicits innate and adaptive anti-melanoma immune responses, resulting in marked suppression of the treated tumors as well as bystander metastatic lesions.

Animals↗
PubMed2001

Direct thrombin inhibition reduces lung collagen, accumulation, and connective tissue growth factor mRNA levels in bleomycin-induced pulmonary fibrosis.

Dramatic activation of the coagulation cascade has been extensively documented for pulmonary fibrosis associated with acute and chronic lung injury. In addition to its role in hemostasis, thrombin exerts profibrotic effects via activation of the major thrombin receptor, protease-activated receptor-1. In this study, we examined the effect of the direct thrombin inhibitor, UK-156406 on fibroblast responses in vitro and on bleomycin-induced pulmonary fibrosis in rats. UK-156406 significantly inhibited thrombin-induced fibroblast proliferation, procollagen production, and connective tissue growth factor (CTGF) mRNA levels when used at equimolar concentration to the protease. Thrombin levels in bronchoalveolar lavage fluid and expression of thrombin and protease-activated receptor-1 in lung tissue were increased after intratracheal instillation of bleomycin. The characteristic doubling in lung collagen in bleomycin-treated animals (38.4 +/- 2.0 mg versus 17.1 +/- 1.4 mg, P < 0.01) was preceded by significant elevations in alpha1(I) procollagen and CTGF mRNA levels (3.0 +/- 0.4-fold and 6.3 +/- 0.4-fold respectively, (P < 0.01), and total inflammatory cell number. UK-156406, administered at an anticoagulant dose, attenuated lung collagen accumulation in response to bleomycin by 35 +/- 12% (P < 0.05), inhibited alpha1(I) procollagen and CTGF mRNA levels by 50% and 35%, respectively (P < 0.05), but had no effect on inflammatory cell recruitment. This is the first report showing that direct thrombin inhibition abrogates lung collagen accumulation in bleomycin-induced pulmonary fibrosis.

Animals↗
PubMed2002

Regulation of Smad3 expression in bleomycin-induced pulmonary fibrosis: a negative feedback loop of TGF-beta signaling.

Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine involved in controlling critical cellular activities including proliferation, differentiation, extracellular matrix production, and apoptosis. TGF-beta signals are mediated by a family of Smad proteins, of which Smad2 and Smad3 are downstream intracellular targets of serine/threonine kinase receptors of TGF-beta. Although Smad2 and Smad3 are crucial for TGF-beta signaling, little is known about the regulation of their expression. In this study, we investigated the expression of Smad2 and Smad3 in an in vivo animal model of lung fibrosis induced by bleomycin. We found that the expression of Smad3 was regulated in lungs during bleomycin-induced pulmonary fibrosis. The decline of Smad3 mRNA was evident at day three of post-bleomycin instillation and the expression of Smad3 continually decreased during the reparative phase of lung injury (days 8 and 12), whereas the expression of Smad2 showed little change after bleomycin administration. We further investigated whether the expression of Smad3 was regulated by TGF-beta in an in vitro lung fibroblast culture system. Our results show an immediate translocation of Smad3 protein from the cytoplasm to the nucleus and a delayed down-regulation of Smad3 mRNA by TGF-beta in lung fibroblasts. These studies provide direct evidence for a differential regulation of Smad3 expression that is distinct from that of Smad2 during bleomycin-induced pulmonary fibrosis and suggest a ligand-induced negative feedback loop that modulates cellular TGF-beta signaling.

Active Transport, Cell Nucleus↗
PubMed1998

Bleomycin associated pulmonary toxicity: is perioperative oxygen restriction necessary?

PURPOSE: We delineate predictive factors of pulmonary morbidity in patients who receive combination chemotherapy with bleomycin and undergo surgical resection of residual disease, and establish updated guidelines for perioperative management. MATERIALS AND METHODS: A total of 77 patients with high volume stage II to IV nonseminomatous germ cell tumors underwent 97 major surgical procedures a mean of 6.4 months following high dose combination chemotherapy, including bleomycin (mean 437.5 units per 8.2 courses), between 1988 and 1995 at the University of Texas M. D. Anderson Cancer Center. The importance of preoperative pulmonary status, anesthesia time, fraction of inspired oxygen, fluid balance, bleomycin dose, number of acute toxicity episodes, oxygen saturation problems and pulmonary symptoms was examined. Cases were divided into groups according to whether there were postoperative oxygen saturation problems (19) or not (58). RESULTS: There were no significant differences in age, weight, bleomycin dose, number of acute toxicity episodes, cardiac ejection fraction or preoperative pulmonary symptoms between the 2 groups. Restrictive spirometry patterns were seen in 26 of 74 patients (35%), only 9 of whom had postoperative oxygen saturation problems. Mean induction fractional inspired oxygen was 87% (median 100%) for an average of 56 minutes. Intraoperative fractional inspired oxygen averaged 40% for a mean duration of 8.1 hours. Postoperative oxygen saturation problems, consisting of prolonged intubation, pulmonary edema, dyspnea, tachypnea or desaturation requiring diuresis, occurred in 19 patients (25%). Surgery/anesthesia time, amount of blood transfused, estimated blood loss, fluid balance, type of fluid given (all p < 0.0001) and preoperative forced vital capacity (p = 0.012) were significant predictors of postoperative oxygen saturation problems on univariate analysis. On multivariate analysis only the amount of blood transfused, preoperative forced vital capacity and surgical time in descending order remained significant. Maintained intraoperative fractional inspired oxygen was not significant on either analysis. There were no deaths. CONCLUSIONS: Perioperative oxygen restriction in patients treated with bleomycin is not necessary. Intravenous fluid management, including transfusion, appears to be the most significant factor affecting postoperative pulmonary morbidity and overall clinical outcome. In addition, post-chemotherapy forced vital capacity and operative time are significant predictive factors of procedure related pulmonary morbidity.

Adolescent↗
PubMed1982

Vinblastine, actinomycin D, bleomycin, cyclophosphamide and cis-platinum combination chemotherapy in metastatic testis cancer--a 1-year program.

Vinblastine, actinomycin D, bleomycin, cyclophosphamide and cis-platinum were given in 31 men with stage III or bulky stage II malignant germ cell tumors of the testis and no previous chemotherapy, 25 of whom were evaluable. This regimen was given for 1 year and began with 3 successive inductions at 3 to 4-week intervals: 600 mg./m.2 intravenous cyclophosphamide, 4 mg./m.2 intravenous vinblastine, 30 mg. intravenous bleomycin and 1 mg./m.2 intravenous actinomycin D on day 1, followed by continuous 24-hour infusion of 20 mg./m.2 bleomycin per day on days 1 to 3 and 120 mg./m.2 intravenous cis-platinum with mannitol-enhanced diuresis on day 4. Any residual disease was resected 1 month after the third induction. If the resected specimen contained malignant tissue an additional 2 inductions (total 5) were given before brief maintenance with 6 mg./m.2 intravenous vinblastine and 1 mg./m.2 intravenous actinomycin D every 3 weeks for the remainder of 1 year. Complete remission occurred in 23 of 25 evaluable patients (92 per cent) and 20 (80 per cent) remain free of disease with a median followup of more than 27 months. Patients with minimal metastatic deposits and those without teratoma in the testis tumor had high complete remission rates with chemotherapy alone. Patients with advanced disease and with teratoma in the primary tumor benefited more frequently from the combined approach. Myelosuppression was the major potentially serious toxic effect. Vinblastine, actinomycin D, bleomycin, cyclophosphamide and cis-platinum were superior to prior vinblastine, actinomycin D and bleomycin programs because higher complete remission rates were achieved with shorter duration of treatment and lesser disability.

Adolescent↗
PubMed1991

Oxygen-exacerbated bleomycin pulmonary toxicity.

Bleomycin is an antineoplastic agent with potential for producing pulmonary toxicity, attributed in part to its free radical-promoting ability. Clinical and research experiences have suggested that the risk of bleomycin-induced pulmonary injury is increased with the administration of oxygen. We report a case in which the intraoperative administration of oxygen in the setting of previous bleomycin therapy contributed to postoperative ventilatory failure. Our patient recovered with corticosteroid therapy. Physician awareness of a potential interaction between oxygen and bleomycin may help reduce the morbidity and mortality related to bleomycin therapy.

Acute Disease↗
PubMed1998

Induction of mosaic sex-linked recessive lethals in the different germ cell stages of Drosophila melanogaster by bleomycin.

The mutagenicity of bleomycin was studied in the different stages of spermatogenesis in Drosophila melanogaster. Following the injection of 2 microliters of 0.1 micrograms/ml of the chemical into young wild-type males, complete and mosaic sex-linked recessive lethals were scored by the Muller-5 method in five successive broods, mainly representing the different stages of spermatogenesis. The delayed mutagenic effect of the chemical was measured by the proportion of mosaic progeny produced. The results showed that bleomycin significantly increased the proportions of both complete and mosaic lethals in the broods representing the meiotic and pre-meiotic stages, but did not show any significant increase in these proportions in the broods representing the sperms and spermatids. The sizes of the mutated areas in the F1 gonads represented by the proportions of lethal-bearing females in F2 mosaic cultures were small, indicating that the genetic instabilities induced by bleomycin were transformed into actual mutations in later zygotic divisions. The significant divisions. The significant production of mosaic progeny in the F4 generation of the treated males showed that the mosaic F1 females produced by bleomycin were able to produce further mosaic progeny and suggested that bleomycin-induced instabilities can be transmitted as such for many future generations.

Animals↗
PubMed1982

Studies on the chemical reactivity of copper bleomycin.

The copper(II) complex of the clinically used antitumor agent bleomycin (Blm) has cytotoxic as well as antitumor properties. To understand the relationship of the bleomycin ligand, copper bleomycin, and other possible metal complexes of this agent, kinetic studies of the formation of Cu(II)Blm, ligand substitution reactions of CuBlm with ethylenediaminetetraaletic acid, and the redox reaction of CuBlm with thiols have been completed and interpreted along with previous studies of the thermodynamic stability of Cu2+ with bleomycin. Cu(II)Bm is found to be kinetically and thermodynamically stable in ligand substitution processes and is only slowly reduced and dissociated by sulfhydryl reagents. The rate constant of reduction of the complex by 2-mercaptoethanol (2-ME) at pH 7.4 and 25 degrees C is 9.5 X 10(-3) M-1 sec-1, explaining the inhibition of Fe2+-dependent strand scission of DNA by Cu2+ in the presence of 2-ME. CuBlm forms in preference to Fe(II)Blm and cannot be reduced and dissociated rapidly enough by thiols to liberate Blm and form the reactive iron complex. In agreement with the observed chemical stability of CuBlm, it is also shown that the complex is stable in human plasma and in the presence of Ehrlich cells suspended in ascites fluid. Interestingly, little CuBlm enters these cells to carry out cytotoxic reactions. Finally, it is shown that both Cu2+ and Zn2+, at equivalent concentrations to Fe2+, effectively inhibit the strand scission of DNA by Fe(II)Blm plus oxygen. However, at substoichiometric amounts of Cu2+, the ferroxidase activity of Blm enables the drug to remain effective in the strand-scission reaction, despite the lowered Cu-free Blm/Fe2+ ratio. These results are discussed in light of the proposed mechanism of action of bleomycin.

Animals↗
PubMed1981

Iron--dioxygen-dependent changes to the biological activities of bleomycin.

Antitumor antibiotic bleomycin can bind to and degrade DNA, both in vivo and in vitro. This DNA damaging property in vitro can be related to its ability to chelate ferrous ions under aerobic conditions leading to the formation of "active oxygens," which are thought to be directly responsible for the damage. At present, evidence points to the hydroxyl radical formed by an iron-catalyzed Haber-Weiss reaction as the free radical most likely to be involved in this damage. When these same reactions occur in the absence of DNA, the free radicals then damage the bleomycin molecule, resulting in changes to its DNA-degrading activity, antibacterial properties, and chemical composition. Attempts to protect both bleomycin and DNA with a variety of specific and nonspecific scavengers have been unsuccessful, with several even showing pro-oxidant activity towards the iron-dependent damage. Only the metal chelators were effective inhibitors of bleomycin-iron-dependent damage to DNA. The damaged bleomycin lost some 50% of its ability to degrade DNA in vitro. This activity was closely paralleled by a loss in antibacterial activity against two different strains of bacteria.

Animals↗
PubMed1984

Enhancement of N-bis(2-hydroxypropyl)nitrosamine-initiated lung tumor development in rats by bleomycin and N-methyl-N-nitrosourethane.

Potential modification of N-bis(2-hydroxypropyl)nitrosamine (DHPN)-induced lung carcinogenesis by bleomycin and N-methyl-N-nitrosourethane (MNUT) was investigated in male F344 rats. Rats were given 0.2% DHPN for 1 week followed by a weekly i.p. injection of either bleomycin at 2.0 mg/kg body wt or of MNUT at a dose of 1.0 mg/kg body wt for 35 weeks. Animals given DHPN followed by solvent administration alone, either saline or 0.02% ethanol and animals given bleomycin or MNUT without DHPN pretreatment were served as controls. Bleomycin treatment increased the incidence of cancer, whereas hyperplasia, adenoma and cancer of the lung were all significantly elevated after MNUT administration. MNUT alone induced low incidences of lung tumors. Bleomycin also increased the incidence of papillary or nodular hyperplasia of the urinary bladder while it inhibited the development of thyroid tumors. MNUT, however, did not affect tumor development in other organs.

Adenocarcinoma↗
PubMed1999

Effect of age and caloric restriction on bleomycin-chelatable and nonheme iron in different tissues of C57BL/6 mice.

The objective of this study was to test the hypothesis that the widely observed age-associated increase in the amounts of macromolecular oxidative damage is due to an elevation in the availability of redox-active iron, that is believed to catalyze the scission of H2O2 to generate the highly reactive hydroxyl radical. Concentrations of bleomycin-chelatable iron and nonheme iron were measured in various tissues and different regions of the brain of mice fed on ad libitum (AL) or a calorically restricted (to 60% of AL) diet at different ages. The concentrations of these two pools of iron varied markedly as a function of tissue, age, and caloric intake. There was no consistent ratio between the amounts of nonheme and the bleomycin-chelatable iron pools across these conditions. Nonheme iron concentration increased with age in the liver, kidney, heart, striatum, hippocampus, midbrain and cerebellum of AL animals, whereas bleomycin-chelatable iron increased significantly with age only in the liver. Amounts of both nonheme and bleomycin-chelatable iron remained unaltered during aging in the cerebral cortex and hindbrain of AL mice. Caloric restriction had no effect on iron concentration in the brain or heart, but caused a marked increase in the concentration of both bleomycin-chelatable and nonheme iron in the liver and the kidney. The results do not support the hypothesis that accumulation of oxidative damage with age, or its attenuation by CR, are associated with corresponding variations in redox-active iron.

Aging↗
PubMedDate not supplied

Bleomycin sclerosis of pelvic lymphoceles.

PURPOSE: To describe the results of postoperative pelvic lymphocele treatment by means of percutaneous drainage and sclerosis with bleomycin. MATERIALS AND METHODS: Four patients underwent treatment of pelvic lymphoceles by percutaneous tube drainage followed by instillation of bleomycin under fluoroscopic guidance at a concentration of 1 unit/mL. Bleomycin instillation was repeated at weekly intervals until the tube output was less than 10 mL per day. Three of four patients underwent unsuccessful sclerosis previously with alcohol, doxycycline, or povidone iodine. RESULTS: Lymphocele drainage was reduced to less than 10 mL per 24 hours after bleomycin sclerosis in all patients. Three patients required two sessions, and the fourth patient required three sessions. No patient developed recurrent symptoms suggesting reaccumulation of lymph during an average follow-up period of 11 months (range, 6-18 months). No complications related to percutaneous lymphocele drainage or sclerosant therapy were encountered. CONCLUSION: Percutaneous intracavitary instillation of bleomycin may be considered as an alternative to surgery in patients who have undergone unsuccessful lymphocele sclerosis with other agents.

Adult↗
PubMedDate not supplied

Site-specific cleavage of RNA and DNA by complementary DNA--bleomycin A5 conjugates.

Bleomycin displays clinical chemotherapeutic activity, but is so nonspecifically toxic that it is rarely administered. It was therefore of interest to determine whether bleomycin could be directed to cleave RNA or DNA at a specific site by conjugation to a complementary oligonucleotide. A 15 nt MYC complementary oligodeoxynucleotide (HMYC55) bearing a 5' bleomycin A5 (Blm) residue was designed to base-pair with nt 7047-7061 of human MYC mRNA. Reactivity of the Blm-HMYC55 conjugate (and mismatch controls) with a MYC mRNA 30-mer, a MYC DNA 30-mer, and a MYC 2'-O-methyl RNA 30-mer, nt 7041-7070, was analyzed in 100 microM FeNH(4)SO(4), 50 mM beta-mercaptoethanol, 200 mM LiCl, 10 mM Tris-HCl, pH 7.5, at 37 degrees C. Cleavage of the substrate RNA or DNA occurred primarily at the junction of the complementary DNA-target RNA duplex, 18-22 nt from the 5' end of the RNA. Reaction products with lower mobility than the target RNA or DNA also formed. Little or no reaction was observed with more than three mismatches in a Blm-oligodeoxynucleotide conjugate. Neither the short RNA or DNA cleavage fragments nor the low mobility products were observed in the absence of Fe(II), or the presence of excess EDTA. The target RNA was also cleaved efficiently by bleomycin within a hybrid duplex with a preformed single-nucleotide bulge in the RNA strand. New Blm-oligodeoxynucleotide conjugates containing long hexaethylene glycol phosphate based linkers between oligodeoxynucleotide and bleomycin were designed to target this bulge region. These conjugates achieved 8-18% cleavage of the target RNA, depending on the length of the linker. Blm-oligodeoxynucleotide conjugates thus demonstrated sequence specificity and site specificity against RNA and DNA targets.

Binding Sites↗
PubMed1985

DNA damage and growth inhibition in cultured human cells by bleomycin congeners.

Bleomycin is hypothesized to cause cell growth inhibition and cell death via DNA cleavage. We have attempted to determine if net DNA cleavage is directly related to growth inhibition by measuring whether both parameters vary in parallel. Of primary importance to these studies was use of several bleomycin congeners. We have shown that these congeners vary in their abilities both to inhibit cell growth and to cause DNA damage. Bleomycin B2, tallysomycin, and phleomycin were the most potent growth inhibitors, and bleomycin B2 caused the most DNA damage. N-Acetylbleomycin A2 was inactive in both assays. The net amount of DNA damage measured at two levels of growth inhibition was compared for each congener and was found to vary widely among the congeners. Similarly, the degree of growth inhibition at a given level of submaximal DNA damage was found to vary widely when individual congeners were compared to each other. Hence, growth inhibition and net DNA damage due to bleomycin are not directly correlated with each other when individual congeners are compared to each other.

Bleomycin↗
PubMed1985

Copper-bleomycin has no significant DNA cleavage activity.

In contrast to a very recent report [Ehrenfeld, G. M., Rodriguez, L. O., Hecht, S. M., Chang, C., Basus, V. J., & Oppenheimer, N. J. (1985) Biochemistry 24, 81-92], the present careful reexamination demonstrated that copper-bleomycin systems have no significant DNA cleavage activity. In the presence of dithiothreitol, the bleomycin-Cu(II) complex showed little activity for DNA degradation. The DNA strand scission by the Cu(I)-bleomycin-dithiothreitol system was remarkably depressed by deferoxamine rather than by bathocuproine, suggesting the effect of trace amounts of contaminating iron in the experiments. It seems highly unlikely that the DNA breakage activity due specifically to the Cu(I)-bleomycin complex system is substantially strong. Our results indicate that the metal really relevant to the DNA cleavage by bleomycin is iron not copper.

Bacteriophage phi X 174↗
PubMed1985

DNA methylation diminishes bleomycin-mediated strand scission.

Three DNA duplexes differing substantially in sequence were derived from pBR322 plasmid DNA and supercoiled SV40 DNA by digestion with appropriate restriction endonucleases. Following treatment with the restriction methylase HhaI (recognition sequence: GCGC) or HhaI and HpaII (CCGG), the unmethylated and methylated DNAs were compared as substrates for the antitumor agent bleomycin. Bleomycin-mediated strand scission was shown to diminish substantially at a number of sites in proximity to the methylated cytidine moieties, especially where multiple sites had been methylated within a DNA segment of limited size. Detailed analysis of the DNA substrates revealed that both strands of DNA within a methylated region became more refractory to cleavage by bleomycin and that the protective effect could extend as many as 14 base pairs in proximity to the 5-methylcytidine moieties. Among the methylated DNA segments that became more resistant to bleomycin cleavage was a HpaII site of SV40 DNA, methylation of which has previously been shown to diminish the synthesis of the major late viral capsid protein following microinjection into Xenopus laevis oocytes. Study of the cleavage reaction at varying salt levels suggested that diminished bleomycin strand scission may be due, at least in part, to local conformational changes of the DNA to Z form (or other non-B-form structures). The results are generally consistent with the hypothesis that one mechanism for the expression of selective therapeutic action by certain DNA damaging agents could involve the recognition of specific methylation patterns.

Base Sequence↗