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V M Kosma

Publications and source records attributed to V M Kosma.

At least 73 records · Page 4Linked to original sources
PubMed1999

Expression of cyclins A and D and p21(waf1/cip1) proteins in renal cell cancer and their relation to clinicopathological variables and patient survival.

We have studied 118 renal cell carcinomas to analyse the expressions of cyclins A and D1 and p21(waf1/cip1), and their relationship to clinical and histopathological parameters as well as to clinical outcome. Cyclins A and D1 and cyclin-dependent kinase inhibitor p21 (waf1/cip1) were not expressed in normal renal tissue. Staining signals of cyclin D1 and p21(waf1/cip1) were always nuclear but cyclin A was also expressed in the cytoplasm of the tumour cells. The mean (range) fractions of cyclin A, cyclin D1 and p21(waf1/cip1)-positive tumour cells were 2.2% (range 0-20%), 23.3% (range 0-90%) and 6.8% (range 0-70%) respectively. The expression of cyclin A was related to venous invasion, high nuclear grade, high mitotic rate, high Ki-67 and high PCNA expressions (P < or = 0.006 for all). The expression of cyclin D1 was linked with age over 65 years, low nuclear grade and high p53 expression (P < or = 0.05 for all). An inverse correlation was present between p21(waf1/cip1) and cyclin D1 (P = 0.011). Cyclin A predicted survival in the entire study group (P = 0.0014), in T1-4/N0-2/M0 (P = 0.0007) and in T1-2/N0/M0 tumours (P = 0.0007). Cyclin A was also a powerful predictor of disease-free survival in T1-4/N0/M0 (P = 0.0027) tumours (P = 0.0007). Cyclin D1 and p21(waf1/cip1) were not significantly related to survival or disease-free survival in any of the groups. In the entire material the independent prognostic factors were the presence of distant metastases (relative risk (RR) 5.16, P < 0.001), T category (RR 2.68, P < 0.001), Ki-67 expression (RR 1.02, P = 0.026) and cyclin A expression (RR 1.12, P = 0.001). The independent predictors in T1-4/N0/M0 tumours were T-category (RR 2.67, P = 0.001) and cyclin A (RR 1.21, P < 0.001), and in T1-2/N0/M0 tumours the only significant predictor was cyclin A (RR 1.19, P = 0.0002). In renal cell carcinoma, cyclin A is a powerful and independent prognostic factor in all clinical stages of the disease, whereas cyclin D1 and p21(waf1/cip1) have no prognostic value.

Adult↗
PubMed1999

p22/WAF1 expression in human colorectal carcinoma: association with p53, transcription factor AP-2 and prognosis.

p21/WAF1 expression was studied in a series of 162 colorectal carcinoma patients and its relation to p53- and activator protein (AP)-2 expressions and to stage as well as survival was assessed. p21 expression was moderate or intense in 33% of the tumours, and 53% of the tumours had moderate or strong p53 staining intensity. Eighty-nine percent of the tumours showed a weak cytoplasmic AP-2 signal. As expected, p21 and p53 stainings were inversely related to each other (P < 0.001). There was a significant positive association between p21 and AP-2 expression levels (P= 0.01). p21 intensity and percentage were higher in Dukes' A and B stages (P< 0.001). The cancer-related survival and recurrence-free survival (RFS) rates were significantly lower among patients with a low signal for p21 (P< 0.001) and low p21 percentage in tumour epithelium (P < 0.001). High p53 staining intensity in tumour epithelium predicted poor survival (P = 0.01) and RFS (P = 0.003). In the multivariate analysis, p21 percentage distribution independently predicted cancer-related survival in all cases, and p21 expression intensity in T1-4/N0-3/M0 and T1-3/N0/M0 cases. p21 percentage distribution was an independent predictor of RFS in all and T1-3/N0/M0 cases. AP-2 staining did not reach any prognostic significance. These results suggest that the immunohistochemical detection of cyclin-dependent kinase inhibitor p21 could be used to predict more precisely the outcome of colorectal cancer patients.

Adenocarcinoma↗
PubMed1999

Association of p53, K-ras and proliferating cell nuclear antigen with rat lung lesions following exposure to simulated nuclear fuel particles.

Expression of p53, K-ras, and proliferating cell nuclear antigen (PCNA) and mutations of p53 and K-ras genes in lung lesions of Han/Wistar rats were investigated by immunohistochemistry and direct DNA sequencing following a long-term exposure of animals to neutron-activated UO2 particles. The p53 protein was overexpressed in all five malignant tumors, in 62% of benign tumors, and in 42% of hyperplastic lesions examined. K-ras protein and PCNA levels were only slightly elevated in all types of lung lesions. In three malignant tumors a C-->T transition was detected in codon 288 (human 290) of the p53 gene, but this mutation was not present in seven other tumors analyzed. No mutations were detected in codons 12/13 and 61 of the K-ras gene in any of the five tumors analyzed. Our findings suggest that K-ras overexpression is a rare alteration, whereas p53 protein overexpression (sometimes associated with mutated p53 gene), as assessed with the CM5 antibody, is a relatively common phenomenon in hot particle-induced preneoplastic and neoplastic rat lung lesions.

Animals↗
PubMed1999

Reduced expression of alpha catenin is associated with poor prognosis in colorectal carcinoma.

AIMS: To investigate alpha catenin expression in surgically resected human colorectal cancers to evaluate its prognostic value during long term follow up. METHODS: Immunohistochemistry was used to compare the expression of alpha catenin with conventional prognostic factors in 187 colorectal cancer patients treated in Kuopio University Hospital and followed up for a mean of 14 years. The hypothesis that the intensity of expression of alpha catenin and its distribution in cancer cells is correlated with survival was tested with the long-rank test, hazard ratios, and their confidence intervals. RESULTS: Uniform membranous alpha catenin staining localised to the intercellular borders was observed in 46% of the tumours; 55% of all tumours had either heterogeneous or negative alpha catenin expression, and staining intensity was either negative or weak in 42% of the tumours. The cancer related and recurrence-free survival rates were lower among patients with a weak alpha catenin intensity in tumour epithelium (p < 0.001), a low fraction of positive tumour cells (p < 0.001), and an additional cytoplasmic accumulation of alpha catenin (p < 0.001). In multivariate analysis, the intensity of alpha catenin expression in tumour epithelium predicted cancer related survival independently; alpha catenin localisation in tumour epithelium was an independent prognostic factor of recurrence-free survival in the group as a whole and in the T1-3N0M0 tumour subgroup. CONCLUSIONS: A low proportion of positive carcinoma cells, additional cytoplasmic accumulation of alpha catenin, and reduced expression intensity in tumour epithelium predict a poor survival rate. The results suggest that alpha catenin has prognostic significance in colorectal cancer.

Adult↗
PubMed1999

Downregulation of p21/WAF1 is related to advanced and dedifferentiated laryngeal squamous cell carcinoma.

AIM: To analyse p21/WAF1 expression and its relation to p53, apoptosis, cell proliferation, clinicopathological characteristics, and patient survival in human laryngeal squamous cell carcinoma. METHODS: Primary tumours for analyses were obtained from 172 patients with complete follow up data. All patients were treated between 1975 and 1995. Immunohistochemistry was used to evaluate the expression of p21/WAF1, bcl-2, and p53 proteins. The proliferative activity was determined using Ki67 and PCNA antibodies as well as volume corrected mitotic count (M/V index). Volume corrected apoptotic count (A/V index) was determined using an enzymatic in situ cell death detection kit based on the TUNEL method. RESULTS: High p21 expression was significantly related to high p53 and normal bcl-2 expressions as well as low mitotic count. No association was noticed between p21 expression and apoptotic rate. A significant inverse correlation between p21 expression and advanced stage and poor differentiation was observed, but p21 expression showed no correlation with survival. CONCLUSIONS: The expression of p21 was associated with tumour stage, histopathological grade, node status, and mitotic count, which may indicate a role for p21 in the progression of laryngeal squamous cell carcinoma.

Adult↗
PubMed1999

Stent placement versus percutaneous transluminal angioplasty of human carotid arteries in cadavers in situ: distal embolization and findings at intravascular US, MR imaging and histopathologic analysis.

PURPOSE: To compare endovascular stent placement with percutaneous transluminal angioplasty (PTA) of carotid arteries with respect to distal embolization and findings at intravascular ultrasonography (US), magnetic resonance (MR) imaging, and histopathologic analysis. MATERIALS AND METHODS: PTA was performed in situ in one carotid artery, and stent placement was performed in the other, in ten cadavers (age range, 57-82 years; mean age, 68 years) with severe atherosclerosis by using fluoroscopic and intravascular US guidance. The carotid artery was connected to a pressurized tubing system in which a pulsatile pump circulated water. The effluent water was collected during the interventions, and after filtration and staining, the embolic material was analyzed histologically. After the interventions, the arteries were excised and 1.5-T spin-echo MR imaging was performed. RESULTS: No difference in severity of distal embolization during stent placement versus during PTA was found. The embolic particles were composed mainly of intimal strips and cellular constituents of the atherosclerotic plaques. MR imaging accurately depicted postinterventional changes, and the findings correlated closely with those of intravascular US and histopathologic analysis. CONCLUSION: Although stent placement and PTA were associated with equal distal embolization, the smooth surface and fully patent arterial lumen depicted at intravascular US and MR imaging postinterventionally may indicate that stent placement is preferable to PTA.

Aged↗
PubMed1999

Nitric oxide and proinflammatory cytokines in nasal lavage fluid associated with symptoms and exposure to moldy building microbes.

Epidemiological data indicate that living or working in a moldy building is associated with increased risk of respiratory symptoms and disease related to inflammatory reactions, but biochemical evidence linking cause and effect is still scarce. The staff working in a mold-contaminated school, and a reference group without such exposure, were studied. Nasal lavage was performed and health data were collected with a questionnaire at the end of the spring term, after a 2.5-mo summer vacation, and at the end of the fall term. Here we show that concentrations of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and nitric oxide (NO) in nasal lavage fluid were significantly higher in the exposed than in the control subjects at the end of the first exposure period. These inflammatory mediators decreased to reference group concentrations during the period when there was no exposure and the production of NO and IL-6 increased again during the reexposure in the fall term. Reports of cough, phlegm, rhinitis, eye irritation, and fatigue paralleled the changes in the measured inflammatory markers. These results point to an association between inflammatory markers in the nasal lavage fluid, the high prevalence of respiratory symptoms among the occupants, and chronic exposure to molds in the indoor environment.

Adult↗
PubMed1999

Non-suppressed thyrotropin and elevated thyroglobulin are independent predictors of recurrence in differentiated thyroid carcinoma.

OBJECTIVE: Although in most cases differentiated thyroid carcinoma (DTC) responds to surgery and radioiodine (RaI) therapy, some patients will have recurrence and eventually cancer-related death. However, although various prognostic factors of DTC have been identified (e.g. staging, suppressed thyrotropin), none of the previous studies have assessed simultaneously their role in multivariate analysis. DESIGN AND METHODS: In this retrospective population-based study, we reviewed the clinicopathological data of 254 DTC patients treated in eastern Finland during the years 1976-1995, for clinical characteristics, primary treatment, follow-up and cancer recurrence. Tumor stage was based on pathological tumor-node-metastasis (pTNM) classification, and histopathological specimens were re-evaluated. RESULTS: DTC recurrence occurred in 33 patients (13%). In univariate analyses, the predictors of recurrence were older age (>60 years, P<0.05), follicular tumor type (P<0.01), pTNM classification system (P<0.05) and post-ablative radioiodine uptake outside the neck (P<0.05). Non-suppressed serum thyrotropin (TSH) and elevated serum thyroglobulin (>3 microg/l) measured one year after operation were both related to tumor recurrence (P<0.05 and P<0.001 respectively). In multivariate analysis the independent predictors for recurrence were both elevated thyroglobulin (P<0.001) and non-suppressed TSH (P<0.05) independent of histology, pTNM stage and RaI uptake. Adjusted risk ratio for recurrence of DTC for unsuppressed thyrotropin was 2.3, for elevated thyroglobulin 14.0 and, if both conditions were present, the risk ratio increased to 45.1. CONCLUSION: Our results suggest that both non-suppressed serum TSH and elevated serum thyroglobulin are related to an increased risk of DTC recurrence independent of tumor type and pTNM stage.

Adenocarcinoma, Follicular↗
PubMed1998

Cytoplasmic accumulation of alpha-catenin is associated with aggressive features in laryngeal squamous-cell carcinoma.

Aberrations in the function of alpha-catenin (alpha-cat), the anchoring protein of E-cadherin, are believed to cause dysfunction of the cadherin-catenin complex, leading to disturbed cell-cell adhesion. It has been suggested that expression of alpha-cat in human tumours might be a better indicator of aggressive phenotype than expression of E-cadherin. The value of alpha-cat as a prognostic marker in laryngeal squamous cell carcinoma (LSCC) is unclear. To determine the potential prognostic significance of alpha-cat, paraffin-embedded samples from 159 patients with invasive carcinoma left in the section and with long-term follow-up were evaluated immuno-histochemically for alpha-cat expression, and the results were related to histopathological grade, tumour stage and survival. Two patterns of staining were observed: pure membranous staining (57%) and membranous staining with cytoplasmic involvement (43%). Cytoplasmic involvement of alpha-cat was associated with dedifferentiation, advanced tumour stage and nodal status. In addition, supra-glottic tumours showed more often cytoplasmic involvement of alpha-cat than glottic tumours. Patients with cytoplasmic involvement appeared to have a trend towards poor overall survival, though without statistical significance. These results suggest that cytoplasmic involvement of alpha-cat is associated with aggressive behaviour and metastatic phenotype of LSCC.

Adult↗
PubMed1998

Expression of hyaluronan in normal and dysplastic bronchial epithelium and in squamous cell carcinoma of the lung.

A series of 85 lung/bronchial tissue samples from 76 patients consisting of normal, metaplastic and dysplastic epithelium and different types of lung carcinomas were analyzed for the distribution of hyaluronan (HA), using a biotinylated hyaluronan binding complex as an HA-specific probe. The normal pseudo-stratified columnar bronchial epithelium was either negative for HA or displayed a weak staining around the basal cells. The epithelia of serous and mucous bronchial glands were HA negative whereas the submucosal connective tissue was strongly positive. In metaplastic, dysplastic and carcinoma in situ lesions the whole epithelium from basal to uppermost cells expressed HA on plasma membranes. Epithelial HA was also found in squamous cell carcinomas, but not in adenocarcinomas, carcinoid tumors or small cell carcinomas of the lung. Whereas epithelial HA was present in all lesions of the squamous cell type, the staining intensity displayed great local variability in 50% of the cases with severe dysplasia, carcinoma in situ and squamous cell carcinomas. In squamous cell carcinomas, such an irregular staining pattern was significantly associated with poor differentiation. Our results indicate that the expression of HA in different bronchial lesions and lung tumors is restricted to those showing squamous cell differentiation, being absent from other types of lung carcinomas. The increase of HA depleted areas in poorly differentiated squamous cell carcinomas emphasizes the important role of HA in tumor differentiation. HA on carcinoma cell surface may influence tumor growth and metastatic behavior.

Adenocarcinoma↗
PubMed1998

Tumor cell-associated hyaluronan as an unfavorable prognostic factor in colorectal cancer.

Hyaluronan (HA) is a linear high molecular weight extracellular polysaccharide. It is thought to be involved in mitosis and the enhancement of wound healing, tumor invasion, and metastasis. Because its clinical relevance in cancer has not been explored, we scored HA in colorectal adenocarcinoma and studied its relationship with patient survival. A specific probe prepared from cartilage proteoglycan aggregates was used to stain paraffin-embedded tumor samples from 202 colorectal adenocarcinoma patients treated in Kuopio University Hospital and followed up for a mean of 14 years. The hypothesis that the percentage of HA-positive carcinoma cells (HA%) and HA intensity in cancer cells correlated with survival was tested with the log-rank test, hazard ratios, and their confidence intervals. Ninety-three % of tumors had at least a proportion of carcinoma cells positive for HA. HA intensity in tumor epithelium was stronger in Dukes' stages C and D tumors and in high-grade tumors. The cancer-related survival rate was lower among patients with strong HA intensity in tumor epithelium (P < 0.001) and high HA% (P < 0.001). Recurrence-free survival was also shorter in patients with an intense signal for HA (P = 0.001) and high HA% in tumor epithelium (P = 0.04). HA intensity in tumor epithelium independently predicted survival and recurrence-free survival (Cox's analysis). We conclude that a high proportion of HA-positive cancer cells and high intensity of the HA-signal predicts a poor survival rate. The abnormal expression of HA in the neoplastic colon epithelial cells is suggested to provide a distinct advantage for invasive growth and metastasis.

Adenocarcinoma↗
PubMed1998

Expression of CD44 standard and variant-v6 proteins in transitional cell bladder tumours and their relation to prognosis during a long-term follow-up.

The expression of the standard CD44 (CD44s) and its v6 isoform (CD44v6) was analysed immunohistochemically in 173 cases of transitional cell bladder cancer. The results of immunohistochemical analyses were related to established prognostic factors and clinical follow-up data. The expression intensity of CD44s in non-basal tumour cells was significantly related to TN classification, S-phase fraction (SPF), mitotic index, grade, density of tumour infiltrating lymphocytes. The expression intensity of CD44v6 in non-basal tumour cells was inversely related to DNA ploidy, SPF, and mitotic index. The expression intensity of CD44v6 in basal tumour cells was also inversely related to T-category, grade, papillary status, DNA ploidy, SPF, and mitotic index. Strong expression of CD44s in non-basal tumour cells was related to unfavourable outcome in univariate analysis (p = 0.008), whereas the strong expression of CD44v6 in both non-basal cells (p = 0.005) and basal cells (p = 0.0008) was related to high survival probability. In multivariate survival analysis, the expression intensity of CD44v6 was independently related to favourable outcome in muscle invasive tumours, while in superficial tumours, CD44s was an independent prognostic factor. The results suggest that the expression of CD44s and CD44v6 is associated with malignant features and prognosis in bladder cancer.

Adult↗
PubMed1998

Clinical relevance of p53 index and expression of proliferating cell nuclear antigen and Ki-67 in gastric cancer.

The prognostic value of the immunohistochemical expression of p53 protein, proliferating-cell nuclear antigen (PCNA) and Ki-67 antigen was evaluated in a series of 116 stage I-II gastric cancer patients. The staining for p53 protein (staining frequency and intensity) in malignant cells was expressed as a p53 index. Similarly, the staining frequency and intensity for PCNA and Ki-67 were evaluated. The p53 index was independent of the stage and differentiation grade, but significantly related to DNA ploidy, S-phase fraction and mitotic activity. A high p53 index was a sign of inferior survival, compared to a low or intermediate index. p53-negative tumours were also associated with poor survival. In a multivariate analysis, only the depth of tumour infiltration and the presence of nodal metastases were independent prognostic factors in stage I-II gastric cancer. PCNA expression and Ki-67 antigen expression were not related to the stage, ploidy, proliferative activity or p53 expression, and they had no impact on survival. The results indicate that p53 protein expression may be of prognostic significance in gastric cancer, while PCNA and Ki-67 antigen expression have no predictive value.

Adult↗
PubMed1998

Mitotic rate and S-phase fraction as prognostic factors in stage I cutaneous malignant melanoma.

Clinical data from 369 patients with clinical stage I cutaneous malignant melanoma treated in Kuopio University Hospital district between 1974 and 1989 with a mean follow-up of 6.4 years were analysed. Clinical parameters, histology, DNA index, S-phase fraction (SPF) and mitotic indices [mitotic activity index (MAI) and volume-corrected mitotic index (M/V index)] were correlated with the outcome of the disease to establish their value as predictors of stage I cutaneous malignant melanoma. In univariate survival analyses, bleeding, gender, tumour thickness, level of invasion according to Clark, TNM category, MAI, M/V index and SPF were the most significant predictors of recurrence-free (RFS) and overall survival. In Cox's multivariate analysis, tumour thickness (P = 0.0021), bleeding (P = 0.0106) and M/V index (P = 0.0058) predicted poor RFS in the 259 patients available for the analysis. Poor overall survival was predicted by MAI (P = 0.0002), bleeding (P = 0.004), SPF (P = 0.009) and male gender (P = 0.034). The present results indicate that mitotic activity index (MAI), volume-corrected mitotic index (M/V index) and S-phase fraction (SPF) are important prognostic factors in addition to the well-established Breslow thickness in stage I cutaneous malignant melanoma.

Adult↗
PubMed1998

Markers of cartilage and synovial metabolism in joint fluid and serum of patients with chondromalacia of the patella.

OBJECTIVE: To further our understanding of the pathogenesis of chondromalacia of the patella (CM), we have studied the release into knee joint fluid and serum, obtained from patients with CM, of molecules associated with the metabolism of joint cartilage matrix and synovium. METHODS: Interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), stromelysin-1 (MMP-3), interstitial collagenase (MMP-1), tissue inhibitor for metalloproteinases-1 (TIMP-1), phospholipase activity A2 (PLA2), hyaluronan (HA), aggrecan fragments (AGN) and antigenic keratan sulfate (KS) were quantified in knee joint lavage fluid from 96 patients with CM; KS and HA also was measured in serum. Chondromalacia was graded on a scale of I to IV according to Outerbridge (1961). The histopathology of the synovial membrane close to the patellofemoral joint was evaluated. Control samples were obtained from nine patients with knee pain presenting with arthroscopically normal knee joints. RESULTS: The concentrations of MMP-3, MMP-1 and TIMP-1 proteins in joint lavage fluid were increased in advanced (grade IV) CM, compared with controls. Levels of MMP-1 in lavage fluid correlated with the severity of CM (r = 0.38, P < 0.01) and MMP-1 and MMP-3 concentrations correlated with each other (r = 0.45, P < 0.001). TIMP-1 was elevated in grade IV CM compared with grades II and III CM (P < 0.02, P < 0.01). Interleukins (IL-1 alpha, IL-1 beta and IL-6) showed no significant change in CM. The lavage fluid level of PLA2 increased with the severity of CM (r = 0.40, P < 0.001). Serum KS was higher in CM IV than in controls (P = 0.05), while lavage fluid KS concentration was elevated in CM I (P = 0.04). There were no differences in the lavage fluid levels of AGN and HA between the different study groups. Synovium showed slight or moderate histological signs of inflammation in 9% of CM patients. CONCLUSION: The changes in the release and activity of these marker molecules from serum and synovial fluid may reflect changes in the metabolism of articular cartilage and synovium in CM, that are consistent with those observed in early-stage tibiofemoral cartilage changes in OA.

Adult↗
PubMed1998

Expression of CD44 and variant proteins in human colorectal cancer and its relevance for prognosis.

BACKGROUND: CD44 is a cell adhesion molecule often expressed in the form of various splice variants. The role of standard CD44 isoform (CD44s) and its variants in colorectal carcinogenesis is partly conflicting. Therefore, we compared the expression of CD44s (hermes-3) and its splice variants (v3 and v6) with traditional prognostic factors in 194 colorectal cancer patients treated at Kuopio University Hospital and followed up for a mean of 14 years. METHODS: Formalin-fixed, paraffin-embedded tissue sections from 194 patients with colorectal carcinoma were examined immunohistochemically to detect the expression of different forms of CD44. The hypothesis that CD44s, CD44v3, and CD44v6 expression intensities and distribution in cancer cells correlated with survival was tested with the log-rank test, hazard ratios, and their confidence intervals. RESULTS: In high-grade tumours CD44s and CD44v6 expression intensities and CD44s percentages were stronger than in low-grade tumours. CD44v6, CD44v3, and CD44s expression intensities in tumour epithelium were also stronger in Dukes C and D tumours than in A and B tumours. In the univariate survival analysis patients with strong CD44s, CD44v3, and CD44v6 expression intensities in tumour epithelium had lower cancer-related survival than the patients who had weak CD44s, CD44v3, and CD44v6 expression intensities. Recurrence-free survival was also shorter in patients with intense signals for CD44v3 and CD44v6 in tumour epithelium. In the multivariate analysis the CD44v6 expression intensity in tumour epithelium predicted independently both cancer-related and recurrence-free survival in T1-4N0-3M0 and T1-3N0M0 cases. In addition, the CD44v3 expression intensity in tumour epithelium was a significant predictor of RFS in T1-3N0M0 cases. CONCLUSIONS: These results strongly suggest that the CD44 splice variants v6 and v3 have prognostic significance in colorectal cancer.

Adult↗
PubMed1998

Effects of 50 Hz magnetic fields on UV-induced skin tumourigenesis in ODC-transgenic and non-transgenic mice.

PURPOSE: To study the possible role of 50 Hz magnetic fields (MF) in UV-induced skin tumourigenesis using a sensitive animal model. MATERIALS AND METHODS: Transgenic mice (line K2) over-expressing the human ornithine decarboxylase (ODC) gene and their non-transgenic littermates were exposed for 10.5 months to UV-only or a combination of UV and a continuous (100 microT) or an intermittent MF with varying intensity (1.3-130 microT). RESULTS: Both MF exposure and transgenicity enhanced the onset rate of macroscopically detectable tumours, but the effect was statistically significant only for the MF exposure (p < 0.015). The number of animals bearing malignant tumours was low and similar in all exposure groups. Epidermal cysts (EC) appeared to be strongly associated with both MF exposure and high ODC activity (transgenic animals). However, EC are not known to be associated with carcinogenesis. The UV-only or combined UV and MF exposure did not affect the ODC activities measured at the end of the exposure. CONCLUSIONS: These results support the proposed tumour-promoting effect of MF, but do not suggest an important role for increased ODC activity in this process.

Animals↗