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Expression and autoregulation of transforming growth factor α receptor mRNA in small-cell lung cancer cell lines
16 (1996)
1.29; CL 1.03-1.60). The PCMRfor nasal cavity/sinuscancer was also found to bca significantly increased, 5.18 (CL 2.37-11.30). A cluster of bladder cancer was seen among black workers from one facility, (PCMP., 3.30; CL, 1.42-6.51). Despite the cessation of exposure, former chromium workers remain at significantly increased risk of lung cancer. Although there have been case reports of nasal cavity/sinus cancer in association with chromium exposure, this is the first epidemiologic study to report a significant increase in these cancers. Limitations in this study include lack of exposure data and lack of information on smoking habits. The lack of increase in other smoking-related diseases besides lung cancer indicates that the increase in lung cancer cannot bc attributed to cigarette smoking. The ongoing elevated risk of lung cancer afler cessation of exposure emphasizes the need for developing early detection tests for lung cancer.
Lung cancer risk in relation to the CYP2El Rsa I genetic polymorphism among African-Americans and Caucasians in Los Angeles County London SJ, Daly AK, Cooper J et al. National Institute, Environmental Health
Services,
PO Box 12233, Research
Triangle
Park,
NC 27709.
Pharmacogenetics 1996;6:151-8. Genetic polymorphisms in the activation or detoxication of carcinogens, such as those in tobacco smoke, may produce differences in individual susceptibility to lung cancer. The cytochrome P450 CYPSE 1 is an enzyme involved in the metabolism of nitrosamines in tobacco smoke. A polymorphism of CYP2El detectable by the restriction enzyme Rsa I may be functionally important because it is located in a putative binding site for the transcription factor HNF-1 and has been associated with higher levels of CYPZEI transcription. It is conceivable that this CYF’ZEl Rsa 1 polymorphism might contribute to differences in susceptibility to lung cancer. We conducted a case-control study of patients with incident lung cancer and population controls in Los Angeles County to examine the association between the CYP2El Rsa I polymorphism and lung cancer risk among African-Americans and Caucasians. Samples of white blood cell DNA sufficient for determination of the CYP2El Rsa I genotype by a polymerase chain reactionbased assay were obtained from 341 cases and 706 controls with data on lifetime smoking history. No subjects were homozygous for the CYPZEI Rsa I rare c2 allele. The rare c2 allele was not associated with an increased risk of lung cancer (adjusted odds ratio, OR = 0.72; 95% confidence interval, Cl = 0.35-1.46). Among the population controls the percentage of subjects carrying the rare c2 allele was lower (p = 0.002) among African-Americans (2%) compared with Caucasians (8%). However, the association between the CYPZE 1 Rsa I genotype and lung cancer risk did not differ between ethnic groups. There was no important association between the CYP2El Rsa I genotype and lung cancer risk in analyses stratified by cell-type, smoking history, gender, cccupational asbestos exposure, and dietary intake of antioxidants vitamin C, vitamin E or be&carotene. Due to the low frequency of the c2 allele in these populations, larger sties would be necessary to rule out a modest association between the CYP2El Rsa I polymorphism and lung cancer risk. Expression and autoregulation of transforming growth factor a receptor mRNA in small-cell lung cancer cell lines Norgaard P, Spang-Thomsen M, Poulsen HS. Section fir Radiation Biology. The Finsen Centez DK-2100, Copenhagen. Br J Cancer 1996;73: 1037-43. In small-cell lung cancer cell lines resistance to growib inhibition by transforming growth factor (TGF)a, was previously shown to correlate with lack of TGFa receptor I (RI) and II @II) proteins. To further investigate the role of these receptors, the expression of mRNA for
I(
105-127
RI, RI1 and beta-glycan @III) was examined. The results showed th loss of RI1 mRNA correlated with TGFa, resistance. In contrast, R and beta-glycan mRNA was expressed by all cell lines, including tho. lacking expression of these proteins. According to Southern blot anal: sis, the loss of type II mRNA was not due to gross structural changes, the gene. The effect of TGFa, on expression 0fTGF-a receptor mRN (receptor autoregulation) was examined by quantitative Northern blo ting in four cell lines with different expression of TGFa receptor pn teins. In two cell lines expressing all three TGFa receptor protein beta-glycan mRNA was rapidly down-regulated and this effect was su tained throughout the 24 h observation period. Rl and RI1 mRNAs we, slightly increased 24 h after treatment. In one cell line sensitive to growl inhibition by TGFa, but lacking beta-glycan expression, and one ce line expressing only beta-glycan and thus TGF-a,-resistant, no autoreg lation of mRNA of either TGFa receptor was demonstrated. The r, sults suggest that TGFa, regulates the expression of its receptors, i particular beta-glycan, and that this effect is dependent on co-exprer sion of beta-glycan, RI and RIl. Induction of benign and maIignant pulmonary tumours in mic with benzo(a)pyrene Km SH, Lee CS. Department ofAnotomy, College of Veterinary Med tine, Chonnam National University, 300 Yongbong-dong, Kwanju 500-757. Anticancer Res 1996;16:465-70.
Puk-kt
Most of the pulmonary tumors induced by chemical carcinogens i mice are pulmonary adenomas. Because of the morphological and bit logical characteristics, the site of origin and the spontaneous occm rence of this type of tumour, the pulmonary adenoma system is gene, ally not considered to be an adequate model for studies designed t elucidate the pathogenesis of human bronchogenic carcinoma. Th present study was carried out to observe the histopathological change in the lung of 4 strains of mice intratracheally instilled with benzc )pyrene(BP). On the other hand for, the carcinogenesis experiment using animals, a method studying the incidence of pulmonary adenom in newborn mice has been generally adopted but this method still need more tban 24 weeks. This experiment was one of the attempts to mak such an experimental period shorter. For the latter experiment, boti inbred A/J and noninbred N:GP(s) newborn mice were used. In th group given intratracheal instillation, squamous cell carcinomas an, adenocarcinomas were induced. Tumous were induced in high inci hence in the lung of A/J and C57BL/6 mice. Squamous cell carcinoma :specially were well differentiated in the A/J mice with a higher inci dence than C57BU6. In the groups given subcutaneous injection, ad equate combinations at week 9 for the application following anti-car cinogenesis assay were the groups of A/J treated with 40 pg (71.09 adenoma incidence) and N:GP(s) mice treated with 500 pg (49.4% ad enoma incidence) of BP These findings suggest that mice appeal ad equate for studies on the pathogenesis of malignant lung tumours am detecting anticarcinogens.
Lung cancer mortaIity among males of Catalonia and Spaia compared with other European countries between 1975 and 1987-1989 Bonfill X, Moreno C, F’mda G, River0 E, Rue M Sew C/in. EpidemioI./ Infomration, Consorci Sabadell (Bamelona).
Iiospitalari
del Pm
Touli, Pm
Touli s/n, 08028
Int J Cancer 19%;65:7514. This study compares the lung -r mortality rates among males in the years 1975-1977 and 1987-1989 in Catalonia and Spaio with other European countries selected for their geographical proximity. Adjusted caIculatIons using the direct method have been made for male lung cancer mortality. Adjusted truncated rates for the age groups O-44,4564 and more than 65 years were also calculated, as well as percent dif-
1.29; CL 1.03-1.60). The PCMRfor nasal cavity/sinuscancer was also found to bca significantly increased, 5.18 (CL 2.37-11.30). A cluster of bladder cancer was seen among black workers from one facility, (PCMP., 3.30; CL, 1.42-6.51). Despite the cessation of exposure, former chromium workers remain at significantly increased risk of lung cancer. Although there have been case reports of nasal cavity/sinus cancer in association with chromium exposure, this is the first epidemiologic study to report a significant increase in these cancers. Limitations in this study include lack of exposure data and lack of information on smoking habits. The lack of increase in other smoking-related diseases besides lung cancer indicates that the increase in lung cancer cannot bc attributed to cigarette smoking. The ongoing elevated risk of lung cancer afler cessation of exposure emphasizes the need for developing early detection tests for lung cancer.
Lung cancer risk in relation to the CYP2El Rsa I genetic polymorphism among African-Americans and Caucasians in Los Angeles County London SJ, Daly AK, Cooper J et al. National Institute, Environmental Health
Services,
PO Box 12233, Research
Triangle
Park,
NC 27709.
Pharmacogenetics 1996;6:151-8. Genetic polymorphisms in the activation or detoxication of carcinogens, such as those in tobacco smoke, may produce differences in individual susceptibility to lung cancer. The cytochrome P450 CYPSE 1 is an enzyme involved in the metabolism of nitrosamines in tobacco smoke. A polymorphism of CYP2El detectable by the restriction enzyme Rsa I may be functionally important because it is located in a putative binding site for the transcription factor HNF-1 and has been associated with higher levels of CYPZEI transcription. It is conceivable that this CYF’ZEl Rsa 1 polymorphism might contribute to differences in susceptibility to lung cancer. We conducted a case-control study of patients with incident lung cancer and population controls in Los Angeles County to examine the association between the CYP2El Rsa I polymorphism and lung cancer risk among African-Americans and Caucasians. Samples of white blood cell DNA sufficient for determination of the CYP2El Rsa I genotype by a polymerase chain reactionbased assay were obtained from 341 cases and 706 controls with data on lifetime smoking history. No subjects were homozygous for the CYPZEI Rsa I rare c2 allele. The rare c2 allele was not associated with an increased risk of lung cancer (adjusted odds ratio, OR = 0.72; 95% confidence interval, Cl = 0.35-1.46). Among the population controls the percentage of subjects carrying the rare c2 allele was lower (p = 0.002) among African-Americans (2%) compared with Caucasians (8%). However, the association between the CYPZE 1 Rsa I genotype and lung cancer risk did not differ between ethnic groups. There was no important association between the CYP2El Rsa I genotype and lung cancer risk in analyses stratified by cell-type, smoking history, gender, cccupational asbestos exposure, and dietary intake of antioxidants vitamin C, vitamin E or be&carotene. Due to the low frequency of the c2 allele in these populations, larger sties would be necessary to rule out a modest association between the CYP2El Rsa I polymorphism and lung cancer risk. Expression and autoregulation of transforming growth factor a receptor mRNA in small-cell lung cancer cell lines Norgaard P, Spang-Thomsen M, Poulsen HS. Section fir Radiation Biology. The Finsen Centez DK-2100, Copenhagen. Br J Cancer 1996;73: 1037-43. In small-cell lung cancer cell lines resistance to growib inhibition by transforming growth factor (TGF)a, was previously shown to correlate with lack of TGFa receptor I (RI) and II @II) proteins. To further investigate the role of these receptors, the expression of mRNA for
I(
105-127
RI, RI1 and beta-glycan @III) was examined. The results showed th loss of RI1 mRNA correlated with TGFa, resistance. In contrast, R and beta-glycan mRNA was expressed by all cell lines, including tho. lacking expression of these proteins. According to Southern blot anal: sis, the loss of type II mRNA was not due to gross structural changes, the gene. The effect of TGFa, on expression 0fTGF-a receptor mRN (receptor autoregulation) was examined by quantitative Northern blo ting in four cell lines with different expression of TGFa receptor pn teins. In two cell lines expressing all three TGFa receptor protein beta-glycan mRNA was rapidly down-regulated and this effect was su tained throughout the 24 h observation period. Rl and RI1 mRNAs we, slightly increased 24 h after treatment. In one cell line sensitive to growl inhibition by TGFa, but lacking beta-glycan expression, and one ce line expressing only beta-glycan and thus TGF-a,-resistant, no autoreg lation of mRNA of either TGFa receptor was demonstrated. The r, sults suggest that TGFa, regulates the expression of its receptors, i particular beta-glycan, and that this effect is dependent on co-exprer sion of beta-glycan, RI and RIl. Induction of benign and maIignant pulmonary tumours in mic with benzo(a)pyrene Km SH, Lee CS. Department ofAnotomy, College of Veterinary Med tine, Chonnam National University, 300 Yongbong-dong, Kwanju 500-757. Anticancer Res 1996;16:465-70.
Puk-kt
Most of the pulmonary tumors induced by chemical carcinogens i mice are pulmonary adenomas. Because of the morphological and bit logical characteristics, the site of origin and the spontaneous occm rence of this type of tumour, the pulmonary adenoma system is gene, ally not considered to be an adequate model for studies designed t elucidate the pathogenesis of human bronchogenic carcinoma. Th present study was carried out to observe the histopathological change in the lung of 4 strains of mice intratracheally instilled with benzc )pyrene(BP). On the other hand for, the carcinogenesis experiment using animals, a method studying the incidence of pulmonary adenom in newborn mice has been generally adopted but this method still need more tban 24 weeks. This experiment was one of the attempts to mak such an experimental period shorter. For the latter experiment, boti inbred A/J and noninbred N:GP(s) newborn mice were used. In th group given intratracheal instillation, squamous cell carcinomas an, adenocarcinomas were induced. Tumous were induced in high inci hence in the lung of A/J and C57BL/6 mice. Squamous cell carcinoma :specially were well differentiated in the A/J mice with a higher inci dence than C57BU6. In the groups given subcutaneous injection, ad equate combinations at week 9 for the application following anti-car cinogenesis assay were the groups of A/J treated with 40 pg (71.09 adenoma incidence) and N:GP(s) mice treated with 500 pg (49.4% ad enoma incidence) of BP These findings suggest that mice appeal ad equate for studies on the pathogenesis of malignant lung tumours am detecting anticarcinogens.
Lung cancer mortaIity among males of Catalonia and Spaia compared with other European countries between 1975 and 1987-1989 Bonfill X, Moreno C, F’mda G, River0 E, Rue M Sew C/in. EpidemioI./ Infomration, Consorci Sabadell (Bamelona).
Iiospitalari
del Pm
Touli, Pm
Touli s/n, 08028
Int J Cancer 19%;65:7514. This study compares the lung -r mortality rates among males in the years 1975-1977 and 1987-1989 in Catalonia and Spaio with other European countries selected for their geographical proximity. Adjusted caIculatIons using the direct method have been made for male lung cancer mortality. Adjusted truncated rates for the age groups O-44,4564 and more than 65 years were also calculated, as well as percent dif-