Zymogen-poor acinic cell carcinoma of the soft palate with high-grade transformation.

Acinic cell carcinoma is an uncommon malignant salivary gland tumour accounting for approximately 6-7% of all salivary gland neoplasms. The key diagnostic feature of acinic cell carcinoma is the presence of acinar cell differentiation characterised by cytoplasmic zymogen secretory granules. This tumour shows a variety of growth patterns, including solid, microcystic, follicular and papillary cystic patterns. Acinic cell carcinoma is typically a cytologically low-grade malignancy. Acinic cell carcinomas with high-grade transformation (HGT) are exceedingly rare and are reported to have a more aggressive clinical course than conventional acinic cell carcinoma. This is a case report of this uncommon entity with high-grade transformation arising on the soft palate in a 64-year-old woman.

Karyotype patterns, clinical features, and parental ages of three predominant live born autosomal trisomies of Northeast Malaysia.

Chromosomal abnormality is one of the causes of congenital disorders among newborns. Despite aneuploidy being the major cause of first trimester miscarriages, very few aneuploidies such as trisomies of chromosomes 13, 18 and 21 survive to birth. The results of 4,064 patients referred for cytogenetic analysis at Human Genome Centre, Universiti Sains Malaysia, Kelantan, Malaysia between 2008 and 2019 were reviewed. We retrospectively investigated the karyotype patterns, clinical features and parental ages of the three common live-born autosomal trisomies such as trisomy 13, trisomy 18 and trisomy 21. The relative frequency of cases with the total sample received and cultured was calculated in each group and compared with those reported elsewhere. Between 2008 and 2019, a total of 1034 live-born trisomic cases which accounted for 25.4% of the 4064 total referred cases and 73.7% of 1403 suspected trisomy cases, were identified, with age ranging from newborns to 57 years. Down syndrome was the commonest aneuploidy (857 cases; 21.1%) followed by Edwards syndrome (133 cases; 3.3%) and Patau syndrome (44 cases; 1.1%). The number of diagnosed cases for each of the trisomies was fairly stable from year to year. About two-thirds of both maternal and paternal ages were ≥ 35 years. This is the first cytogenetic report on the common live-born autosomal trisomies in the North-Eastern region of Malaysia. The prevalence of trisomies 21 was found to be higher compared to an earlier study in the North-Western region of Malaysia, wherein also, advanced maternal age was a significant risk factor.

The effect of platelet-rich plasma as a scaffold in regeneration/revitalization endodontics of immature permanent teeth assessed using 2-dimensional radiographs and cone beam computed tomography: a randomized controlled trial.

AIM: To assess the outcomes of platelet-rich plasma as a scaffold in regenerative/revitalization endodontics (RET) using cone beam computed tomography (CBCT) and 2-dimensional radiographs. METHODOLOGY: Twenty-six healthy patients with mean age of 12.66 ± 4.47, and immature permanent anterior teeth with necrotic pulps, were randomly allocated to two groups, whereby RET was performed using platelet-rich plasma (PRP, test group) and blood clot (BLC, control group). Changes in root length (RL), root dentinal thickness (RDT), apical foramen width (AFW) and radiographic root area (RRA), were assessed using both radiographic methods, whilst changes in periapical area diameter (PAD) were assessed using CBCT, over a period of 12 months. T-test and chi-square/Fisher's exact tests were used to compare continuous and categorical data between BLC and PRP groups, respectively. Changes in RL, RDT, AFW, RRA and PAD were examined by comparing the two groups (PRP versus BLC) using multilevel modelling, considering the clustering effect of repeated measures of several teeth originating from the same participant. RESULTS: Changes in RL, RDT, AFW, RRA and PAD, over time, were found to be significant for both groups. There was, however, no difference between the RET techniques (PRP versus BLC), using both radiographic and CBCT methods. The results of both assessment techniques (CBCT and 2-dimensional radiographic methods) were highly consistent (overall ICC ranged between 0.80 and 0.94). In addition, a significant effect of baseline PAD was found on RL, RRA and AD at 12 months (RL effect = -0.68, P < 0.001; RRA effect = -1.91, P = 0.025; AD effect = 0.08, P = 0.024). CONCLUSION: The current study highlights successful and comparable clinical and radiographic outcomes of RET techniques using PRP and BLC. Standardized and calibrated 2-dimensional radiographic assessment was as effective as CBCT in assessing RET outcomes; therefore, the routine use of CBCT in RET is not recommended. Although an effect of baseline periapical lesion diameter on root development outcomes, at 12 months, were observed, more studies are recommended in order to assess such an effect.

Clinical implications of conventional cytogenetics, fluorescence in situ hybridization (FISH) and molecular testing in chronic myeloid leukaemia patients in the tyrosine kinase inhibitor era - A review.

Chronic myeloid leukaemia (CML) provides an illustrative disease model for both molecular pathogenesis of cancer and rational drug therapy. Imatinib mesylate (IM), a BCR-ABL1 targeted tyrosine kinase inhibitor (TKI) drug, is the first line gold standard drug for CML treatment. Conventional cytogenetic analysis (CCA) can identify the standard and variant Philadelphia (Ph) chromosome, and any additional complex chromosome abnormalities at diagnosis as well as during treatment course. Fluorescence in situ hybridization (FISH) is especially important for cells of CML patients with inadequate or inferior quality metaphases or those with variant Ph translocations. CCA in conjunction with FISH can serve as powerful tools in all phases of CML including the diagnosis, prognosis, risk stratification and monitoring of cytogenetic responses to treatment. Molecular techniques such as reverse transcriptase-polymerase chain reaction (RT-PCR) is used for the detection of BCR-ABL1 transcripts at diagnosis whereas quantitative reverse transcriptase-polymerase chain reaction (qRTPCR) is used at the time of diagnosis as well as during TKI therapy for the quantitation of BCR-ABL1 transcripts to evaluate the molecular response and minimal residual disease (MRD). Despite the excellent treatment results obtained after the introduction of TKI drugs, especially Imatinib mesylate (IM), resistance to TKIs develops in approximately 35% - 40% of CML patients on TKI therapy. Since point mutations in BCR-ABL1 are a common cause of IM resistance, mutation analysis is important in IM resistant patients. Mutations are reliably detected by nested PCR amplification of the translocated ABL1 kinase domain followed by direct sequencing of the entire amplified kinase domain. The objective of this review is to highlight the importance of regular and timely CCA, FISH analysis and molecular testing in the diagnosis, prognosis, assessment of therapeutic efficacy, evaluation of MRD and in the detection of BCR-ABL1 kinase mutations which cause therapeutic resistance in adult CML patients.

Prevalence of Group A beta-haemolytic Streptococcus isolated from children with acute pharyngotonsillitis in Aden, Yemen.

OBJECTIVES: To estimate the prevalence of Group A beta-haemolytic streptococcus (GAS) and non-GAS infections among children with acute pharyngotonsillitis in Aden, Yemen, to evaluate the value of a rapid diagnostic test and the McIsaac score for patient management in this setting and to determine the occurrence of emm genotypes among a subset of GAS isolated from children with acute pharyngotonsillitis and a history of acute rheumatic fever (ARF) or rheumatic heart disease (RHD). METHODS: Group A beta-haemolytic streptococcus infections in school-aged children with acute pharyngotonsillitis in Aden, Yemen, were diagnosed by a rapid GAS antigen detection test (RADT) and/or GAS culture from a throat swab. The RADT value and the McIsaac screening score for patient management were evaluated. The emm genotype of a subset of GAS isolates was determined. RESULTS: Group A beta-haemolytic streptococcus pharyngotonsillitis was diagnosed in 287/691 (41.5%; 95% CI 37.8-45.3) children. Group B, Group C and Group G beta-haemolytic streptococci were isolated from 4.3% children. The RADT had a sensitivity of 238/258 (92.2%) and specificity of 404/423 (95.5%) against GAS culture. A McIsaac score of ≥4 had a sensitivity of 93% and a specificity of 82% for confirmed GAS infection. The emm genotypes in 21 GAS isolates from children with pharyngitis and a history of ARF and confirmed RHD were emm87 (11), emm12 (6), emm28 (3) and emm5 (1). CONCLUSION: This study demonstrates a very high prevalence of GAS infections in Yemeni children and the value of the RADT and the McIsaac score in this setting. More extensive emm genotyping is necessary to understand the local epidemiology of circulating strains.

Genome-wide analysis of oral squamous cell carcinomas revealed over expression of ISG15, Nestin and WNT11.

BACKGROUND: Multistep pathways and mechanisms are involved in the development of oral cancer. Chromosomal alterations are one of such key mechanisms implicated oral carcinogenesis. Therefore, this study aims to determine the genomic copy number alterations (CNAs) in oral squamous cell carcinoma (OSCC) using array comparative genomic hybridization (aCGH) and in addition attempt to correlate CNAs with modified gene expression. MATERIALS AND METHODS: Genome-wide screening was performed on 15 OSCCs using high-density aCGH. On the basis of pathway analysis, three genes (ISG15, Nestin and WNT11) which mapped to CNA regions were selected for further evaluation of their mRNA expression using quantitative reverse transcriptase PCR (qRT-PCR). RESULTS: Copy number alterations were observed on multiple genomic regions, including amplifications on 1p, 3q, 5p, 6p, 7p, 8q, 9q, 11q, 12q, 16p, 18p and deletions on 3p, 7q, 8p, 11q, 19q and 20q. Among the three selected genes, ISG15 had the highest mRNA expression level with a 22.5-fold increase, followed by Nestin with a 4.5-fold increase and WNT11 with a 2.5-fold increase. CONCLUSIONS: This study has identified several major CNAs in oral cancer genomes and indicated that this correlates with over expression of the ISG15, WNT11, and Nestin genes.

Association between POLG and XRCC1 gene polymorphisms and keratoconus occurrence among Egyptian patients. / Asociación entre polimorfismos de los genes POLG y XRCC1 y aparición de queratocono entre pacientes egipcios.

BACKGROUND: Keratoconus is a progressive disorder distinguished by thinning of the corneal tissue and bulging forward into a cone-shaped fashion. Yet its etiology, which is multifactorial, despite intensive research remains elusive. Corneal exposure a reactive oxygen species causing oxidative DNA damage has been reported to be associated with KC and therefore suggesting that DNA base excision repair mechanism might lie behind the pathogenesis of the disease. METHODS: We studied the association of three variants in two BER genes (XRCC1 and POLG) and QC occurrence in a cohort of patients from Egypt. Genotyping of the three variants was performed using PCR and restriction enzymes analysis. RESULTS: We observed that A allele and A/A genotype of the c.1196A>G variant in the XRCC1 gene were significantly associated with increased KC occurrence while the G allele was associated with decreased KC occurrence. Similarly, the A/A genotype of the c.-1370T>A polymorphism in the POLG gene and the A allele were associated with increased occurrence of KC, while T/A genotype and the T allele were accompanied with decreased occurrence of KC. On the other hand, no association was observed between the c.580C>T variant in the XRCC1 gene and KC occurrence among the studied group of patients. CONCLUSION: Our results suggest that c.1196A>G variant of the XRCC1 and c.-1370T>A variant of the POLG gene may be involved in KC pathogenesis and might be considered as a genetic risk factors of the disease among Egyptian population.

Human telomerase reverse transcriptase expression in oral carcinogenesis--a preliminary report.

Human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase, is strongly associated with telomerase activity implicated in cellular immortalization and tumorigenesis. In situ detection of hTERT will aid in determining the localization of telomerase positive cells. The aim of this study was to detect hTERT protein expression in multistep oral carcinogenesis using paraffin embedded tissue samples, and to study the relationship of hTERT expression with different histological stages in oral carcinogenesis. Normal (n = 4), hyperplastic (n = 4), dysplastic (n = 4) and neoplastic (n = 10) oral epithelia representing different histological stages in oral carcinogenesis were included in the study. hTERT protein detection was done by immunohistochemistry (IHC) technique. Nuclear staining intensities were noted and the hTERT-labelling index was determined. Dysplastic and neoplastic oral epithelia showed an increased percentage of hTERT positive cells (Grade 4: > 50% positive staining nuclei) with intense staining in the basal, parabasal and superficial layers of the epithelia, unlike normal oral mucosa which showed intense staining only in the basal and parabasal cell layers, which are the normal proliferative progenitor compartments. hTERT protein expression was elevated with the corresponding advancement of the histological stages of oral carcinogenesis, from normal to hyperplasia to dysplasia to carcinoma. There seems to be an upregulation of hTERT protein expression during the progression of oral cancer, therefore, this may indicate the feasibility of IHC detection of hTERT protein in oral carcinogenesis as a potential diagnostic or prognostic marker.

Postcaesarean section uterovesical fistula lined by persistent intermediate trophoblast.

We report a unique case of a postcaesarean section uterovesical fistula lined by intermediate trophoblast. The patient, a 42-year-old woman, presented with cyclical haematuria, and she had had a lower segment caesarean section 1 year previously. She was found to have uterovesical fistula, which was excised. On microscopic examination the fistula tract was lined by intermediate trophoblast characterised by cells with abundant eosinophilic cytoplasm, occasional multiclefted nuclei, and cytoplasmic immunoreactivity for epithelial cytokeratins and human placental lactogen. This finding has not, to our knowledge, been previously described and indicates that the survival of third trimester intermediate trophoblast is independent of pregnancy.

Pathology of endometrium treated with tamoxifen.

AIMS: To determine the type of endometrial abnormalities associated with prolonged tamoxifen treatment and to investigate the correlation between tamoxifen dose and any abnormalities detected. METHODS: Endometria from 19 prospectively collected breast cancer patients treated with tamoxifen were ascribed a pathological diagnosis and the findings compared with those in a control group matched for age and presentation. The abnormalities were related to cumulative tamoxifen dose. RESULTS: The two asymptomatic treated patients had generalised simple endometrial hyperplasia at necropsy. No endometrial abnormalities were seen at necropsy in the two control cases. Of the 17 patients treated with tamoxifen who underwent surgery for gynaecological symptoms, 11 had hyperplastic endometrial polyps characterised by epithelial metaplasias and patchy periglandular condensation of stroma. Two women had primary endometrial malignancies with myometrial invasion, and three women, one of whom had previously presented with a benign polyp, had an endometrial polyp-cancer on a background of hyperplasia. Endometrial malignancies were confined to women who had taken more than 35 g of tamoxifen. The control group included no endometrial polyp-cancers, only one patient with an endometrial polyp, four women with endometrial hyperplasia and four with primary endometrial malignancy. CONCLUSIONS: These findings support a link between prolonged tamoxifen treatment and endometrial malignancy and identify a subgroup of patients--that is, those who have taken more than 35 g of tamoxifen, who may be at increased risk of endometrial cancer. The spectrum of pathological findings in patients treated with tamoxifen suggests that the drug promotes endometrial growth and that endometrial polyps may be an important intermediate step in endometrial carcinogenesis.

Ulcerating rheumatoid nodule of the vulva.

A case of an ulcerating rheumatoid nodule of the vulva in a 76 year old woman with rheumatoid arthritis complicated by Felty's syndrome is reported. The patient presented with a mass in the vulval region. On clinical examination, she had an ulcerated mass associated with inguinal lymphadenopathy. These findings resulted in a clinical diagnosis of invasive carcinoma of the vulva and an excision biopsy was carried out. On microscopic examination, the lesion showed the characteristic features of a rheumatoid nodule with ulceration of overlying epidermis. Adjacent vessels showed inflammation and fibrinoid necrosis of their walls suggestive of a vasculitis. Awareness of the possibility of ulceration in rheumatoid nodules may facilitate diagnosis and avert unduly aggressive treatment.

An unusually aggressive case of endometriosis showing p53 expression.

A 43 year old woman who underwent a hysterectomy and bilateral salpingo-oophorectomy for secondary dysmenorrhoea was found to have bilateral ovarian endometriosis. During the following four years she developed a series of tumour-like vaginal masses, which were locally excised, a pelvic mass causing acute large bowel obstruction, which necessitated an emergency Hartmann's procedure, and a further pelvic mass causing hydronephrosis with a non-functioning kidney. Pathological examination of all the resected specimens showed endometriosis with abundant stromal and glandular elements. Immunoreactivity for p53 protein was detected within endometriotic foci from the initial oophorectomy as well as the latest resection specimens. Immunostaining for p53 may help identify potentially aggressive cases of endometriosis for proactive treatment.

Histogenesis of haemangioblastomas: an immunocytochemical and ultrastructural study in a case of von Hippel-Lindau syndrome.

The cerebellar, retinal, and one of the spinal haemangioblastomas in a case of von Hippel-Lindau syndrome were studied by immunocytochemistry and electron microscopy. The tumours were positive for neurone specific enolase and variably positive for somatostatin, pancreatic polypeptide, and bombesin. Electron microscopy of the cerebellar tumour showed secretory granules with an average diameter of 170 nm. This report is believed to be the first description of neurone specific enolase positivity and polypeptide hormones within the intervascular cells of haemangioblastomas. In the light of these findings it is suggested that haemangioblastomas are tumours of neuroectodermal origin, derived either from neural or neuroendocrine cells.

Cushing's syndrome associated with recurrent endometrioid adenocarcinoma of the ovary.

Ectopic production of adrenocorticotrophic hormone (ACTH) by malignant neoplasms is a well recognised cause of Cushing's syndrome but is extremely rare in ovarian carcinoma. A patient who underwent surgery for ovarian carcinoma followed by a course of chemotherapy is reported. The tumour was a bilateral moderately differentiated endometrioid adenocarcinoma and contained numerous chromogranin immunoreactive endocrine cells as well as small foci of ACTH immunoreactivity. She subsequently presented with Cushing's syndrome in association with extensive pelvic recurrence of the tumour.

Interobserver variation in the diagnosis and grading of dyskaryosis in cervical smears: specialist cytopathologists compared with non-specialists.

AIMS: To compare the assessment of dyskaryosis in cervical smears made by specialist consultant cytopathologists and consultant general histopathologists. METHODS: One hundred and ten cervical smears were circulated to 10 observers from five district general hospital histopathology departments and five major departments of cytopathology. Their responses were analysed by five consultant general histopathologists and five consultant specialist cytopathologists. In 54 of the 110 cases, the histology of a corresponding cervical biopsy specimen was compared with the smear assessments. RESULTS: Specialist cytopathologists were more consistent than non-specialists when diagnosing and grading dyskaryosis. They chose the higher grades of dyskaryosis more frequently than the non-specialists. The cytopathologists recommended referral for colposcopy more frequently, but if they asked for a repeat smear, they wanted it done within three months more frequently than the histopathologists. The specialists were more frequently in agreement with the biopsy grade of intra-epithelial neoplasia than the non-specialists, whose smear diagnoses tended to underestimate the severity of the histopathological abnormality. CONCLUSIONS: This study has shown major differences between specialist and non-specialist cytopathologists in the diagnosis and grading of cervical smears and in the recommended management of patients with abnormal smears. These differences may result in uneven clinical management of women with smear abnormalities. It is therefore important to explore possible strategies for standardising the reporting of cervical smears, such as centralisation of screening services, accreditation in cytopathology for non-specialist consultants, and the value of participation in external quality assessment schemes.

Assay for hepatitis C virus in peripheral blood mononuclear cells enhances sensitivity of diagnosis and monitoring of HCV-associated hepatitis.

Hepatitis C virus (HCV) is a major etiological factor in chronic hepatitis affecting up to 24% of blood donors in Egypt. Since fluctuating levels of HCV RNA loads, including undetectable values, have been frequently observed in sera of chronic hepatitis patients, this study was designed to assess the sensitivity of PCR amplification for the plus- and minus-RNA strands in peripheral blood mononuclear cells (PBMC) compared to single serum PCR assay. Since the latter test detects viremia in only 79.5% of seropositive cases, the highest sensitivity for HCV diagnosis was achieved (93.20% when applying the combined triple test including PCR amplification of plus-strand in serum, together with plus-strand in PBMC and minus-strand in PBMC. The results of this study indicate that the triple test provides significant information on extrahepatic replication of HCV in a sizable sample of seropositive subjects (429 cases) and improves the assessment of HCV viremia. The cost/effectiveness and speed were upgraded by using capillary/air rapid thermal cycler. The use of the triple assay in HCV diagnosis and post-therapy monitoring is recommended.

Prevalence of blindness and low vision in Malaysian population: results from the National Eye Survey 1996.

BACKGROUND: A national eye survey was conducted in 1996 to determine the prevalence of blindness and low vision and their major causes among the Malaysian population of all ages. METHODS: A stratified two stage cluster sampling design was used to randomly select primary and secondary sampling units. Interviews, visual acuity tests, and eye examinations on all individuals in the sampled households were performed. Estimates were weighted by factors adjusting for selection probability, non-response, and sampling coverage. RESULTS: The overall response rate was 69% (that is, living quarters response rate was 72.8% and household response rate was 95.1%). The age adjusted prevalence of bilateral blindness and low vision was 0.29% (95% CI 0.19 to 0.39%), and 2.44% (95% CI 2.18 to 2.69%) respectively. Females had a higher age adjusted prevalence of low vision compared to males. There was no significant difference in the prevalence of bilateral low vision and blindness among the four ethnic groups, and urban and rural residents. Cataract was the leading cause of blindness (39%) followed by retinal diseases (24%). Uncorrected refractive errors (48%) and cataract (36%) were the major causes of low vision. CONCLUSION: Malaysia has blindness and visual impairment rates that are comparable with other countries in the South East Asia region. However, cataract and uncorrected refractive errors, though readily treatable, are still the leading causes of blindness, suggesting the need for an evaluation on accessibility and availability of eye care services and barriers to eye care utilisation in the country.

Von Hippel-Lindau syndrome with microscopic hemangioblastomas of the spinal nerve roots. Case report.

The authors describe a case of von Hippel-Lindau syndrome diagnosed at autopsy in a 49-year-old woman. She died suddenly following hemorrhage from a cerebellar hemangioblastoma. Other autopsy findings included a retinal hemangioblastoma, an adrenal pheochromocytoma, and a clear-cell renal tumor. The case was distinguished by the unexpected finding of multiple microscopic hemangioblastomas of the spinal nerve roots. The case is discussed with emphasis on the incidence of spinal hemangioblastomas in von Hippel-Lindau syndrome.

Identification of proteins in the hamster DNA end-binding complex.

PURPOSE: To identify the protein components of the DNA end-binding complex in hamster cells. MATERIALS AND METHODS: DNA end-binding complexes were identified as follows. Nuclear extracts from Chinese hamster ovary cells (0.5-1.0 microg protein/lane) were incubated with 0.5 ng 32P-labelled probe (144 bp) for 20 min at room temperature in the presence of 1 microg closed circular pUC18 plasmid, a non-specific competitor in a final volume of 20 microl. The electrophoretic mobility of the protein-DNA complexes was analysed by electrophoresis in 5% polyacrylamide gels subjected to autoradiography. Antibodies to various DNA repair-associated proteins were added to the DNA end-binding complex reaction and a supershift identified DNA end-binding complex components. These were confirmed by Western analysis of purified DNA end-binding complex contents. RESULTS: Using both supershift and Western analysis, the following proteins were identified in the DNA end-binding complex: Ku70, Ku80, DNA-dependent protein kinase catalytic subunit, DNA ligase IV, X-ray cross complementing protein 4, meiotic recombination protein 11 (Mre11), Werner's syndrome protein, Bloom's syndrome protein, p53, poly(ADP-ribose) polymerase, replication protein A (RPA) 14, and RPA32, ataxia telangiectasia mutant, c-Abl, Rad50, Nijmegen breakage syndrome protein 1 (NBS1), and DNA ligase III were not detected in the binding complex by any assay. Using a combination of electro-elution and autoradiography, it was estimated that the single DNA end-binding complex contains at least 15 proteins whose molecular weights of the DNA end-binding proteins ranged from 620 to 12 kDa. CONCLUSIONS: A combination of both a supershift assay and Western analysis of the DNA end-binding complexes has identified 12 of at least 15 proteins present in the DNA end-binding complex of Chinese hamster ovary cells. This protein complex contains Mre11, but not Rad50 or NBS1, suggesting that under some conditions, Mre11 might function independently of Rad50 and NBS1.

Nucleotide excision repair proteins and their importance for radiation-enhanced transfection.

PURPOSE: Irradiated cells transfect more efficiently than unirradiated cells because of a radiation-induced increase in plasmid integration. However, the molecular mechanism is unclear. Because of recent observations that nucleotide excision repair (NER) proteins can be involved in certain types of recombination in yeast, it was hypothesized that NER proteins might play a role in this radiation-enhanced integration. MATERIALS AND METHODS: Hamster and human cells with inactivating mutations in NER genes were irradiated at doses from 0 to 6 Gy and then immediately transfected with a linearized selectable marker plasmid. Transfection-enhancement ratios (TERs) were calculated as the ratio of the number of drug-resistant colonies in unirradiated cells to the number of transfectants in irradiated cells, corrected for cytotoxicity from radiation. RESULTS: Transfection into unirradiated rodent cells was unaffected by NER mutation status. Transfection into unirradiated human cells, however, was increased by NER mutation. The TERs were 5 and 100 for CHO and primary human fibroblasts, respectively, after exposure of the cells to 6 Gy. Mutations in ERCC1, XPA, XPB, XPC, XPF, XPG and CSB dramatically reduced TER. Mutations in ERCC1, XPC, XPF, XPG and CSB suppressed transfection so that the TER was significantly below 1. CONCLUSIONS: The mechanism of radiation-enhanced plasmid integration was distinct from that of plasmid integration in unirradiated cells, and NER gene products were critical for enhanced integration to occur.