Excision margins for nonmelanotic skin cancer

Scientific evidence for advisable excision margins for nonmelanotic skin carcinoma is poorly documented. Recommended excision margins vary from 2 to 15 mm. A prospective study was performed on 150 skin lesions excised over a 9-month period in an outpatient facility at the authors' institution. Primary nonmelanotic skin lesions were clinically diagnosed as either basal cell carcinoma (nodular, superficial, infiltrating, or sclerosing) or squamous cell carcinoma (well, moderately, or poorly differentiated). Macroscopic surgical excision margins were individually assessed, measured, and excised. Histopathologic analysis was then independently performed to determine the correct diagnosis and to measure the actual microscopic lateral and deep excision margins.Sixty-one percent of lesions were basal cell carcinoma, 25 percent were squamous cell carcinoma, and 15 percent were benign or premalignant. Diagnostic accuracy was 81 percent for basal cell and 59 percent for squamous cell carcinoma. The average diameter of the basal cell carcinoma was 12.1 mm; 47 percent of these lesions had a diameter of less than 10 mm. The average diameter of the squamous cell carcinoma was 16.9 mm; 26 percent of these lesions had a diameter of less than 10 mm. The mean surgical margin was 4.2 mm (3.2 mm adjusted for shrinkage), whereas the mean microscopic lateral margin was 3.4 mm. Overall, complete excision was achieved for 98 percent of basal cell carcinoma and 100 percent of squamous cell carcinoma. The raw data were analyzed to assess the suitability of 1-, 2-, 3-, or 4-mm surgical excision margins. A 4-mm surgical margin would give a microscopic lateral margin beyond one microscopic high-power field (0.5 mm) in 96 percent of cases of basal cell carcinoma and in 97 percent of cases of squamous cell carcinoma.The authors recommend a 4-mm surgical margin as the optimal treatment for skin lesions clinically diagnosed as basal cell or squamous cell carcinoma that are suitable for excision in an outpatient facility. Well-demarcated lesions, such as a nodular basal cell carcinoma, may be excised with a 3-mm margin.     

Treatment of pyogenic granuloma by shave excision and laser photocoagulation.

We present herein our technique for the management of pyogenic granulomas. Twenty such lesions were treated in 13 patients by shave excision followed by laser photocoagulation of the base. Recurrence was noted in just one case and was successfully treated by repeated laser treatment. The cosmetic results have been uniformly excellent. Shave excision followed by laser photocoagulation is an effective therapeutic alternative to excision and linear closure for the treatment of pyogenic granuloma, one that minimizes scar formation while preserving the ability to confirm the diagnosis.     

B超引导下乳腺肿块粗针穿刺诊断的分析（附120例报道）

目的：探讨B超引导下粗针穿刺在乳腺肿块诊断中的应用意义。方法：使用B超引导下粗针吸取穿刺对120例乳腺肿块进行穿刺活检,然后进行固定,脱水,染色,镜检,结合临床作出病理学诊断。结果：粗针穿刺诊断包括良性病变48例,非典型性导管上皮增生（ADH）32例,导管内癌12例,浸润性癌28例。与后续手术标本病理诊断比较得出确诊率,其中良性病变的诊断率为95．83％（46／48）,ADH的确诊率为75％（24／32）,导管内癌的确诊率为58．33％（7／12）,浸润性癌诊断率为92．86％（26／28）,其中导管内癌与浸润性导管癌和乳腺良性病变的确诊率有显著性差异,而ADH与浸润性导管癌和乳腺良性病变间的确诊率有差异,但本组数据没有统计学意义。结论：超声引导下粗针穿刺对乳腺浸润性癌和良性病变的诊断率较高,但对ADH和原位癌的确诊率较低,有待进一步改进。     

The role of ethylene in the control of cell division in cultured pea root tips: a mechanism to explain the excision effect

Summary A transitory cell division block, or excision effect, occurs in the meristem of roots after excision and transfer to culture medium. This block can be induced, in intact seedling roots, by exogenous treatment with ethylene gas. With continuous treatment, the block is longer and the recovery less than after a 4 hour pulse. In excised roots the excision effect can be eliminated by treatment with an inhibitor of ethylene synthesis (aminoethoxyvinylglycine) or action (silver thiosulfate). These experiments provide evidence to support the hypothesis that ethylene from the wounded end of an excised root is involved in a process resulting in a transitory block in cell cycle progression in the meristem. The implications of this hypothesis are discussed.     

Hypericin as a potential phototherapeutic agent in superficial transitional cell carcinoma of the bladder.

Photodynamic therapy (PDT) involves the local or systemic administration of a photosensitizing drug that, upon light irradiation and presence of oxygen, results in tissue damage such as tumor destruction. Hypericin, a hydroxylated phenanthroperylenequinone, is obtained from Hypericum perforatum plants. Hypericin exhibits a high fluorescence quantum yield, and its presence in the tissue can easily be visualized. Interestingly, when instilled into the human bladders, hypericin selectively accumulates in the bladder carcinoma lesions, with the specificity and sensitivity of detecting CIS reaching up to 98.5 and 93%, respectively. Due to this selective accumulation of hypericin in bladder carcinoma lesions, the compound is now used as a fluorescent diagnostic tool for superficial bladder cancer. However, hypericin is also a photosensitizer with a potent photocytotoxic activity. Taken together, these data indicate that hypericin could be used for whole bladder wall PDT of superficial bladder tumors. This review focuses on the more recent in vitro and in vivo evaluation of hypericin as a photodynamic agent in the treatment of superficial transitional cell carcinoma (TCC) bladder tumors.     

Effects of burn wound excision on bacterial colonization and invasion

Rates of survival after thermal injury have improved in the past two decades, and rates of wound infections and sepsis have decreased during the same period. Early excision has been advocated as one of the major factors, but its safety and efficacy and the exact timing of burn excision are still under debate. It was hypothesized that acute burn wound excision (in the first 24 hours after burning) would be superior to conservative treatment and delayed excision in preventing bacterial colonization and invasion. Twenty consecutive patients with thermal injuries were studied. Twelve patients underwent acute burn wound excision, and eight patients underwent conservative treatment and delayed excision. The second group of patients received topical treatments in another facility and underwent delayed excision after transfer to our service, on postburn day 6. Quantitative bacteriological assessments of the excised wound and biopsy samples of the wound bed, obtained before autografting and/or homografting, were performed. The effects of time on bacterial counts, differences between superficial and deep biopsy samples, and the effects of early versus late debridement were studied. Patients admitted early exhibited bacterial counts of less than 10 bacteria per gram of tissue. Patients in this group did not experience infection or graft loss. Patients admitted late exhibited counts of more than 10 bacteria (p = 0.001, compared with early admission). Three patients in the late excision group experienced infection and graft loss (p < 0.05, compared with the early excision group). Burn wound excision significantly decreased bacterial colonization for all patients (p < 0.001). Greater bacterial colonization and higher rates of infection were correlated with topical treatment and late excision (p < 0.001). It is concluded that burn wound excision significantly reduces bacterial colonization. Patients who undergo topical treatment and delayed burn wound excision exhibit greater bacterial colonization and increased rates of infection. Acute burn wound excision should be considered for all full-thickness burns.     

Biased three-dimensional cell migration and collagen matrix modification

Various tumours can be resected even for cure with complete removal. Surgical excision with a wide margin to ensure complete removal has therefore been suggested as the primary treatment for such lesions. The histological examination of the three-dimensional (3D) excision margins (3D histology) constitutes an important part of the quality control mechanisms in tumour surgery. Understanding histologically relevant properties of the constituents of the microenvironment in tumours and the circumferential portion of non-lesional tissue is therefore critical.Accompanied by the increasing availability of high performance computers in recent decades, there has been a strong movement aiming at the development of mathematical models whose implementations allow in silico simulations of biological reaction networks. Due to its relevance in numerous biological and pathological processes, there have been various attempts to model biased migration of single cells. The model introduced in this paper plays a prominent role insofar as it covers the under-represented 3D case. Moreover, it is uniformly formulated for both two and three dimensions. The velocity of each cell is characterised by a generalised Langevin equation, a stochastic differential equation, where chemotaxis as well as contact guidance are considered to simulate selected aspects of interactions between carcinoma cell groups and fibroblast-like cells.Algorithmic and numeric aspects of the developed equations are detailed in this paper and the results of the simulations are illustrated in different manners to emphasise specific features. A simple test scenario as well as a geometry based on segmentation data of a real histological slide has served for verification of the software. The resulting morphologies closely resemble that of desmoplastic stromal reaction readily identifiable in histological slides of infiltrating carcinoma, and the images can be interpreted in the context of 3D histology.     

Distinction between colloid nodules and follicular neoplasms of the thyroid. Further observations on cell blocks

The differentiation between colloid nodules and follicular neoplasms may be difficult in lesions yielding only microfollicles by fine needle aspiration (FNA). In a retrospective study of 35 follicular lesions, the FNA smears and cell blocks and the excised specimens were reviewed for possible distinguishing features. Columnar cells lining follicles and prominent sinusoidal stroma were seen only in follicular neoplasms; these were more easily appreciated in the cell blocks. Nuclear features and fibrosis were not helpful because they were found in both groups of lesions. Attention to the nuclear morphology was important, however, for the diagnosis of the follicular variant of papillary carcinoma. A repeat FNA might be helpful in obtaining hyperplastic papillae and fragments of dilated follicles for a diagnosis of colloid nodule in half of the cases. A few lesions with predominant microfollicular patterns were even problematic to diagnose on the excised specimens.     

Direct inhibition of excision/synthesis DNA repair activities by cadmium: analysis on dedicated biochips

The well established toxicity of cadmium and cadmium compounds results from their additive effects on several key cellular processes, including DNA repair. Mammalian cells have evolved several biochemical pathways to repair DNA lesions and maintain genomic integrity. By interfering with the homeostasis of redox metals and antioxidant systems, cadmium promotes the development of an intracellular environment that results in oxidative DNA damage which can be mutagenic if unrepaired. Small base lesions are recognised by specialized glycosylases and excised from the DNA molecule. The resulting abasic sites are incised, and the correct sequences restored by DNA polymerases using the opposite strands as template. Bulky lesions are recognised by a different set of proteins and excised from DNA as part of an oligonucleotide. As in base repair, the resulting gaps are filled by DNA polymerases using the opposite strands as template. Thus, these two repair pathways consist in excision of the lesion followed by DNA synthesis. In this study, we analysed in vitro the direct effects of cadmium exposure on the functionality of base and nucleotide DNA repair pathways. To this end, we used recently described dedicated microarrays that allow the parallel monitoring in cell extracts of the repair activities directed against several model base and/or nucleotide lesions. Both base and nucleotide excision/repair pathways are inhibited by CdCl?, with different sensitivities. The inhibitory effects of cadmium affect mainly the recognition and excision stages of these processes. Furthermore, our data indicate that the repair activities directed against different damaged bases also exhibit distinct sensitivities, and the direct comparison of cadmium effects on the excision of uracile in different sequences even allows us to propose a hierarchy of cadmium sensibility within the glycosylases removing U from DNA. These results indicate that, in our experimental conditions, cadmium is a very potent DNA repair poison.     

End results in parotid tumors

Management of parotid tumors can be based on a clinical classification of these lesions as being either "encapsulated" or infiltrating. The Warthin tumor (papillary cystadenolymphomatosum) is a benign encapsulated tumor, often occurring multicentrically or bilaterally especially in the lower pole area of the parotid. It is characterized clinically by its softness and fluctuation in size and a high incidence in elderly men. The so-called "capsule" of well demarcated mixed and mucoepidermoid tumors is represented by a condensation of host fibrous stroma, in the interstices of which tumor cells may be present. The "encapsulated" tumors should be excised with a "shell" of uninvolved parotid tissue. To do this safely, the facial nerve should first be isolated. Total parotidectomy is necessary only if the size of the tumor, the multiplicity of recurrences, or the infiltrating nature of the tumor are such that complete eradication of the primary site must be done. Radical neck dissection is never performed electively except in the small group of nonencapsulated infiltrating primary lesions. In a series of cases of previously untreated parotid tumors treated by the method outlined, the local parotid recurrence rate was less than 1 per cent.     

Characterization of natural killer activity in sponge matrix allografts

NK cell activity, defined by the ability of infiltrating host cells to lyse the YAC-1 tumor target, can be detected in sponge matrix allografts across all genetic barriers tested. Nonspecific tumor cell killing cannot be detected either within bulk populations of host-infiltrating cells or in populations enriched for non-adherent lymphocytes. NK activity is also detected in cells infiltrating a syngeneic sponge matrix graft although to a much lesser extent than an allogeneic graft. NK cell functional activity at the graft site precedes the appearance of alloimmune CTL by several days. The surface phenotype of the NK cell is Thy-1.2+ and L3T4- as determined by depleting the various subpopulations with antibody and C. Systemic treatment of sponge-bearing animals with repeated injections of anti-asialo GM1 (AGM1) results in inhibition of both NK activity and CTL activity recovered from the graft on days 5 to 9 after grafting, but on days 11 to 13 after grafting both NK activity and CTL activity are found within the sponge graft. Treatment of sponge-associated cells with anti-AGM1 in vitro or intrasponge injection of anti-AGM1 at various times after grafting eliminates NK activity more readily than alloimmune CTL activity. The intimate association observed between NK cells and alloimmune CTL at the graft site prompts further investigation into the role of NK cells in the allograft response.     

Mutagenic DNA repair in Escherichia coli. XXI. A stable SOS-inducing signal persisting after excision repair of ultraviolet damage.

Mutations to streptomycin resistance induced by ultraviolet light in Escherichia coli can lose their susceptibility to photoreversing light during excision repair and in the absence of chromosomal replication and protein synthesis, i.e., under conditions where SOS induction cannot occur. Using fusions of lac with sulA and umuC we have shown that after excision of UV damage in the presence of chloramphenicol there is a persisting, relatively stable signal capable of inducing SOS genes when protein sysnthesis is subsequently permitted. The persisting signal is formed roughly in proportion to the square of the UV dose and is about 30% photoreversible. It is suggested that the persisting SOS-inducing signal comprises a UV photoproduct (the target lesion) opposite a gap in the opposing DNA strand, and is formed by excision of one (the ancillary lesion) of a pair of closely opposed photoproducts. Calculations suggest that as few as two or three such configurations in a cell can lead to induction a sulA when protein synthesis is permitted. It is not clear whether these configurations can directly induce the SOS system because of their region of single-stranded DNA or whether the ultimate SOS-inducing signal is a more extensive single-stranded region formed when such configurations encounter a replication fork. Photoproduct/gap configurations have been previously suggested to be potentially mutagenic. UV-induced mutations to streptomycin resistance are mostly at A:T sites and are not photoreversible in fully SOS-induced bacteria in the absence of excision repair, indicating that they are not targeted at cyclobutane-type pyrimidine dimers. In SOS-induced excision-proficient bacteria there is about 39% photoreversibility which is rapidly lost after UV. This photoreversibility is attributed to many ancillary lesions being cyclobutane-type pyrimidine dimers which are excised leading to the exposure of target lesions on the opposing strand which, at these particular sites, are mostly non-photoreversible photoproducts.     

Multicellular Pollen Formation in Cultured Barley Anthers: I. INDEPENDENT DIVISION OF THE GENERATIVE AND VEGETATIVE CELLS

Multicellular pollen units partitioned into embryo- and endosperm-or possibly suspensor-like components are formed in barley (Hordeumvulgare cv. Sabarlis) anthers cultured from spikes excised duringthe free spore phase of microsporogenesis. The embryo-like componentmay be derived from the generative cell, the vegetative cell,or from contributions of both cells, and appears to be usually,though not invariably, haploid. The endosperm- or suspensor-likecomponent is derived from the vegetative cell and rapidly becomesnon-haploid or mixoploid. The initial pattern of division oftensimulates that in the formation of 4-celled and 7-celled embryosacs. The time of excision during the free-spore phase is critical.Partitioning occurs only with excision during the mid-unicellularstage (stage 2) when the nuclei are probably still in the pre-DNAreplication phase, but excision at the early unicellular stage(stage 1) in ineffective and leads to rapid degeneration ofthe spores. With excision at the late-unicellular stage (stage3), independent contribution by the generative cell is blockedand the pollen develops by the known A, B, or C pathways. Temperaturestress given to the excised spikes before culture of the anthersenhances the frequency of partitioned units but is thought notto be causal. It is suggested that the multiplicity of developmentalpathways may have some bearing on whether the plantlets ultimatelyproduced are albino, variegated, or green.     

Substrate specificity of the Escherichia coli Fpg protein (formamidopyrimidine-DNA glycosylase): excision of purine lesions in DNA produced by ionizing radiation or photosensitization.

We have investigated the excision of a variety of modified bases from DNA by the Escherichia coli Fpg protein (formamidopyrimidine-DNA glycosylase) [Boiteux, S., O'Connor, T. R., Lederer, F., Gouyette, A., & Laval, J. (1990) J. Biol. Chem. 265, 3916-3922]. DNA used as a substrate was modified either by exposure to ionizing radiation or by photosensitization using visible light in the presence of methylene blue (MB). The technique of gas chromatography/mass spectrometry, which can unambiguously identify and quantitate pyrimidine- and purine-derived lesions in DNA, was used for analysis of hydrolyzed and derivatized DNA samples. Thirteen products resulting from pyrimidines and purines were detected in gamma-irradiated DNA, whereas only the formation of 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua) and 8-hydroxyguanine (8-OH-Gua) was observed in visible light/MB-treated DNA. Analysis of gamma-irradiated DNA after incubation with the Fpg protein followed by precipitation revealed that the Fpg protein significantly excised 4,6-diamino-5-formamidopyrimidine (FapyAde), FapyGua, and 8-OH-Gua. The excision of a small but detectable amount of 8-hydroxyadenine was also observed. The detection of these products in the supernatant fractions of the same samples confirmed their excision by the enzyme. Nine pyrimidine-derived lesions were not excised. The Fpg protein also excised FapyGua and 8-OH-Gua from visible light/MB-treated DNA. The presence of these products in the supernatant fractions confirmed their excision.(ABSTRACT TRUNCATED AT 250 WORDS)     

Measurement of chemopreventive efficacy in skin biopsies

OBJECTIVE: To explore methods suitable for quantitative assessment of the efficacy of chemopreventive intervention. STUDY DESIGN: High-resolution imagery of nuclei from the suprabasal and basal cell layers of sun-damaged skin were recorded. There were 10 cases. A shave biopsy was taken from an area of clearly evident solar keratosis before and after treatment with 2-difluoromethyl-dlornithine (DFMO) and from the colateral forearm, treated with a placebo. A number of karyometric variables were computed and combined to derive marker features that provided a numeric measure of the degree of nuclear deviation from normal. RESULTS: DFMO treatment was effective overall in reducing the degree of nuclear abnormality seen in the biopsies; in 8 of the 10 cases there was a significant improvement. The placebo-treated arm did not show a statistically different abnormality from the untreated arm. CONCLUSION: Karyometric analysis can provide numeric measures that allow documentation of statistically significant regression of actinic keratotic lesions following treatment with DFMO.     

END RESULTS IN PAROTID TUMORS

Management of parotid tumors can be based on a clinical classification of these lesions as being either “encapsulated” or infiltrating.The Warthin tumor (papillary cystadenolymphomatosum) is a benign encapsulated tumor, often occurring multicentrically or bilaterally especially in the lower pole area of the parotid. It is characterized clinically by its softness and fluctuation in size and a high incidence in elderly men.The so-called “capsule” of well demarcated mixed and mucoepidermoid tumors is represented by a condensation of host fibrous stroma, in the interstices of which tumor cells may be present.The “encapsulated” tumors should be excised with a “shell” of uninvolved parotid tissue. To do this safely, the facial nerve should first be isolated.Total parotidectomy is necessary only if the size of the tumor, the multiplicity of recurrences, or the infiltrating nature of the tumor are such that complete eradication of the primary site must be done.Radical neck dissection is never performed electively except in the small group of nonencapsulated infiltrating primary lesions.In a series of cases of previously untreated parotid tumors treated by the method outlined, the local parotid recurrence rate was less than 1 per cent.     

Characterization of DNA repair in a mutant cell line derived from ICR 2A frog cells that is hypersensitive to non-dimer DNA damages induced by solar ultraviolet radiation

The level of excision repair and the inhibition and recovery of semiconservative DNA synthesis were examined following the induction of non-dimer DNA damages by solar ultraviolet radiation in a mutant cell line, DRP 36, derived from ICR 2A frog cells that is hypersensitive to these lesions. A relatively pure population of non-dimer photoproducts was produced by exposure of cells to the Mylar-filtered solar UV wavelengths produced by a fluorescent sunlamp followed by treatment with photoreactivating light (PRL) which removes most of the small yield of dimers induced by the irradiation. Using a modification of the bromodeoxyuridine (BrdUrd) photolysis assay, that enhances the sensitivity of this assay, it was found that DRP 36 cells perform a significantly lower level of excision repair following the induction of non-dimer DNA damages compared with the ICR 2A cells. In contrast, the level of excision repair of 254-nm-induced dimers was similar in the two cell lines. In addition, the induction of non-dimer damages caused a greater inhibition of DNA synthesis that persisted for a longer period of time in the mutant compared with the parental cells. Hence, these results indicate that the DRP 36 cells are deficient in the repair of at least one type of solar UV-induced non-dimer lesion.     

Recognition and repair of compound DNA lesions (base damage and mismatch) by human mismatch repair and excision repair systems.

Nucleotide excision repair and the long-patch mismatch repair systems correct abnormal DNA structures arising from DNA damage and replication errors, respectively. DNA synthesis past a damaged base (translesion replication) often causes misincorporation at the lesion site. In addition, mismatches are hot spots for DNA damage because of increased susceptibility of unpaired bases to chemical modification. We call such a DNA lesion, that is, a base damage superimposed on a mismatch, a compound lesion. To learn about the processing of compound lesions by human cells, synthetic compound lesions containing UV photoproducts or cisplatin 1,2-d(GpG) intrastrand cross-link and mismatch were tested for binding to the human mismatch recognition complex hMutS alpha and for excision by the human excision nuclease. No functional overlap between excision repair and mismatch repair was observed. The presence of a thymine dimer or a cisplatin diadduct in the context of a G-T mismatch reduced the affinity of hMutS alpha for the mismatch. In contrast, the damaged bases in these compound lesions were excised three- to fourfold faster than simple lesions by the human excision nuclease, regardless of the presence of hMutS alpha in the reaction. These results provide a new perspective on how excision repair, a cellular defense system for maintaining genomic integrity, can fix mutations under certain circumstances.     

Clinico-pathological aspects of immunotherapy by intralesional injection of BCG cell walls or live BCG in bovine ocular squamous cell carcinoma

Summary Bovine ocular squamous cell carcinoma (BOSCC) of clinical stage I, mostly situated in the third eyelid, was chosen as a therapy model for squamous cell carcinoma of the head and neck in humans. Block resection was found to be the best method of treatment. Regression was noticed in 19 out of 30 cows treated intratumourously with a single injection of live BCG or BCG cell wall vaccine, followed by recurrence in 8 cases. In 2 untreated cows, complete lasting regression occurred. Regression was significantly more frequently encountered in intratumourously treated cows than in controls. Regression was associated with a high mitotic index, severe infiltrating growth and small amounts of cellular (lymphoid) infiltration.Metastasis was found in 14 out of 50 cows: 5 in 10 untreated controls, 8 in 30 BCG treated cows and 1 in 10 surgically treated cows. The growth rate of progressively growing untreated and of some treated tumours was not associated with the mitotic index nor with other morphological characteristics tested. The mitotic index was found to be higher in the deep infiltrating layer than in the superficial layer of the primary tumour, suggesting that a single biopsy is not sufficiently representative for cell kinetic studies.Animals were maintained under the guidelines set forth by the Faculty of Veterinary Medicine, State University, Utrecht, The NetherlandsGrant recipient of the Koningin Wilhelmina Fonds (The Netherlands Cancer Foundation)     

Mouse NEIL1 protein is specific for excision of 2,6-diamino-4-hydroxy-5-formamidopyrimidine and 4,6-diamino-5-formamidopyrimidine from oxidatively damaged DNA

A functional homologue of human DNA glycosylase NEIL1 (hNEIL1) in mouse has recently been cloned, isolated, characterized, and named mouse NEIL1 (mNEIL1). This enzyme exhibited specificity for excision of oxidatively modified pyrimidine bases such as thymine glycol, 5,6-dihydrouracil, and 5-hydroxypyrimidines, using oligonucleotides with a single base lesion incorporated at a specific site. It also acted upon AP sites; however, no significant excision of 8-hydroxyguanine was observed [Rosenquist, T. A., Zaika, E., Fernandes, A. S., Zharkov, D. O., Miller, H., and Grollman, A. P. (2003) DNA Repair 2, 581-591]. We investigated the substrate specificity and excision kinetics of mNEIL1 for excision of oxidatively modified bases from high-molecular weight DNA with multiple lesions, which were generated by exposure of DNA in aqueous solution to ionizing radiation. Among a large number of pyrimidine- and purine-derived lesions detected and quantified in DNA, only purine-derived lesions 2,6-diamino-4-hydroxy-5-formamidopyrimidine and 4,6-diamino-5-formamidopyrimidine were significantly excised. This finding establishes that mNEIL1 and its functional homologue hNEIL1 possess common substrates, namely, 2,6-diamino-4-hydroxy-5-formamidopyrimidine and 4,6-diamino-5-formamidopyrimidine. Measurement of excision kinetics showed that mNEIL1 possesses equal specificity for these two formamidopyrimidines. This enzyme also excised thymine-derived lesions thymine glycol and 5-hydroxy-5-methylhydantoin, albeit at a much lower rate. A comparison of the specificity and excision kinetics of mNEIL1 with other DNA glycosylases shows that this enzyme is as efficient as those DNA glycosylases, which specifically remove the formamidopyrimidines from DNA.