of 1 /1
124 Abstracts/Lung Cancer 10 (1993) 123-150 Senm cbolestemi, beta-mmtme, and risk of ltmg cancw Shekelle RB, Tangney CC, Rossof AH, Stander J. School of Public Health. Health Science Cetum, Uniwrsity of Texas. P.O. Box 20186. Houston. TX 77225. Epidemiology 1992$:282-l. This paper bypothe.sixes that be40 -amtene mdiatea the association between low serum cbolesteml and increased risk of lung cancer, predicts that tbe association should be greater in population stratawith low intake of beta-carotene than in those with bigb intake if tbe hypothesis is conwt, and investigates this prediction with data from P 24-year cohort study of 1,960 middle-aged employed -. In the total cohort, serum cholesteml was not related to risk of lung cancer. The relative risk associated with a differenceof -1 .Ommol per liter in serum cholesterol was 1.01 (95% ccrdidace interval of 0.801.27) after adjustment for cigarette smokiag, age, and intake of beta-carotene. In contrast, however. when tbe study group was restricted to mea with intake of beta-carotene <S,OOO (N = 929) or <3,000 IU per day f,N = 272), comparable relative risks were 1.10 and 1.21. respectively. Although the 95% confidence intervals for these relative risks were broad and included unity, the result is consistent with expectation. We conclude that the hypothesis warrants further investigation. A tobacm-spedfic N-nitrmomine or [email protected] smoke condemote comes neoplastic transformation of xmotransplanted human broachbdepitbelialc& Klein-Sunto AJP, limsa T. Momiki S. Garcia-PaI= I, CaamanoJ, Metcalf R et al. Dcpamncnt of Pathology, Far Chase Cancer Cmm, Philadelphia. PA 19111. Pmc Nat1 Acad Sci USA 1992$9:6693-l. Using * xmotmnsplautation system in which immortalized nonhnmorigenic human bmncbial epitbelial cells (BEAS-2B cells) are g~wnindeepithelializednttnchus~t~subcutmeauslytnnsplsnted into atbymic nude mice, we exposed BEAS-2B cells either to cigarette smoke condensate or to the tobacco-specific N-nitrosamiae 4- (methylnitmsamine)-l- (3-pyridyl)-l-butanone. After 6 ma tbe carcino.getl+.xposed BEAS-2B cells were neotdasticallytransformedto in viva to chemicalsexhibited several featureslypical of t&lignani lung cancer cells. such IS increased in viva invasivemw thatwmlated well with enhanced type IV collagenolytic activity, resistance to serum- induced growth inhibition, and increased expression of transforming growth factor 6 and its cellular-membranereceptor. lnvasiveoess, similar to that seen after exposure to phorbol eaten, was also detected after in vitro exposure of BEAS-2B cells to cigarettesmoke wndeasate. Collectively, these data indicate thatcigzirette smoke condensateand N- nitmsamine4-(metbylnitmsamine)-1<3-pyridyl)-l- butanoneinducein viva phenotypic changes in BEAS-2B cells similar to the progressive changes that occur during human lung carcinogenesis. in A/J mice by green tea and its major polyphenol as antioxidants Xu Y, Ho C-T, Amin SG, Han C, Cbuag F-L. American Health Founabion, Valhalla, NYIO595. Cancer Res 1992;52:3875-9. In this study we examined the effects of g- tea and its major components, (-)-epigallocatechingallate (EGCG) and caffeine, on the tobacco- specific nitmsamine 4-(m&ylnitmaminc+1<3-pyridyl)-I- butanone (NNK)- induced lung hmwrigeoesis in A/J mice. We also studied the effects of green tea and EGCG on @-metbylgunine and 8- hydmxydeoxyguanosine (I-GHdGuo) formation in lung tissues caused by NNK treatma 1. Miceweregiven296 tea, 560ppmEGCG. or 1120 ppm caffeine in drinking water for 13 weeks. During this time, NNK (11.65 mg/kg body weight) was administered by gavage three times weekly for 10 weeks from weeks 3 to 12. The bioassay was (e&ted 6weeksafterthelastNNKtreatment.MicetreatedwithNNKdeveloped 22.5 lung adenomas per mouse. whereas NNK-treated mice that drank green tea or EGCG as drinking w&r developed only 12.2 (P < 0.01) and 16.1 (P C 0.05) htmors per mouse, respectively. Mice that drank greenteaorcnffeine solution showed lowerbody weight gains, although little difference in water and diet consumption was noted in these groups. While green tea and EGCG exerted littleeffect on the formation ofOb-methylguanine,ncriticalDNAlesioninNNKlunghrmorigenesis, both treatmeats suppressed the increase of I-GH-dGw levels in mouse lung DNA. The inhibition of S-GHdGuo form&m in lung DNA by gneea tea and EGCG is consistent with their ability to inhibit lung tumorigeaesis by NNK. Because S-GHdGuo is a DNA l&m cawed by oxidativedxmage, thesereadtssuggestthat tbemchanismofinhibition by green tea and EGCG in NNK-induced lung htmorigeoesis is due at least partly to their antioxidantproperties. Reevaluation of silii and lung curer in North Carolins dusty tradea workers Amandus H.E. Castellan R.M. Shy C. Heinemxn E.F. Blair A. DRDS/ NIOSH, 944 C?mmuRidge Road. Morpmn. WV2&505-2888. Am I Ind Med 1992;22:147-53. We previously reportedcmthe lung cancer mortality tbrougb 1983 of 760 males who were diagnosed with silicosis during 1930-1983 by the State of North Camlii’s medicalexamination program for dusty trades workers. ThclungcancerSMR (95% confideaceintaval)w2.6 (1.8- 3.6) among 655 white membersof this group. In this uwer. w renai recl&f&l for pneumoconiosis by 3 ‘B’readen using the &&iLTt) CIassificationLungccerSMRswere 1.7 (O.S-3.1)fortbeentiregmup of 306 whitemales, 2.5 (I. l-4.9) for I43 subjects reclassifiedassimple silicosis, and 1.0 (0.1-3.5) for 96 subjects whose rxdiogmphs were reclassified as IL0 category 0. There were no lung cancerdeaths among 67 subjects whose radiographswar. reclassified as progressive massive fibrosis. Corresponding lung canw SMRs for subjects who bad never ~employedinajobwithexposuretolmowoocc~~arcinogens were 1.2(0.2-4.4)fortbosetr&ssitiedascategoryO,and2.4(1.O-5.0) for those re&ssified es having simple silicasis. The age&justed lung c~ncernlerstio~mwgsubjectswithsimplesilicosiscompPred to those with category 0 was 1.5 (0.4-5.8). Our tindings from this reanalysis, which effectively controls for misclassiticptioa of silicasis due to errors in radiograph interpretation by Noatb Carolinx program waders, offer additional evidence consistent with tbe hypothesis of am association between silicosis and lung cancer in this study group. Compalis6nofltmgmrci-incidarein~ledogsexposedto vuozasyoungadultsorasirmanture~ Griffith WC, Guilmztte ItA, Muggenbwg EA. Inhalation Taricology Rewarch hut., PO Box 58908 Albuquerque, NM 87185. Radial Pmt Dosim 1992;41:101. Beagle dogs were exposed by inhalationeither as immahue ( < 3 months of age) or as young adult (< 13 motttbs of age) dogs to monodispzrsepaticlesof”PuO,. Tbessparticlasan3relativelyinsoluble invivomdtbustbem~jorityofthend~tionQseisdelivmdtotheI~g and associated tissues. As has beea reported previously there - M apparentdifferences in lung rcteaticm assoc.&d with age at exposure. Timedepeadenl radiation dosm to the lung, averaged over the total lung mass, were calculated to take into account the growing lung of tbe immsturedog.‘Ibercwers108imma~~~s~posedtoammodisperse 1.5 m AMAD +icles (74survivorsxre7-lO years xfterexposwe) and 252 young adult dogs exposed to 0.75, 1.5 or 3.0 m AMAD particles (52 survivors are 1l-13 years after exposure). To date, 24 immature dogs have died with lung carcinomas at doses of 2.5 to 83 Gy and 104 young adult dogs have died with lung carcinomasxt doses of 3.2 to 89 Gy. The lung carcinoma incidence rates for the hvo study groups were canpa& using a Con pmpcational hazards model with a time- dependentdose. AcommmbPselineincid~centewrc:uscdsothntrisLs would be estimated relative to the same baseline. No statistically significant difference (P > 0.30) was found be@veen the immxtwe and tbe young adult dogs in how their lung cprcinoau incidmce rates bueased with radiation dose. Tbis suggests that there is not *unique mdioseasitivity attributable to a puticle irradiation of x growing lung. General mortality and respiratory cancer among a cobwt of male chemical workers in California Burchtiel CM, Cartmill JB, Axe FD. Bond Go. Dcponmenr of

Serum cholesterol, beta-carotene, and risk of lung cancer

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124 Abstracts/Lung Cancer 10 (1993) 123-150

Senm cbolestemi, beta-mmtme, and risk of ltmg cancw Shekelle RB, Tangney CC, Rossof AH, Stander J. School of Public Health. Health Science Cetum, Uniwrsity of Texas. P.O. Box 20186. Houston. TX 77225. Epidemiology 1992$:282-l.

This paper bypothe.sixes that be40 -amtene mdiatea the association between low serum cbolesteml and increased risk of lung cancer, predicts that tbe association should be greater in population strata with low intake of beta-carotene than in those with bigb intake if tbe hypothesis is conwt, and investigates this prediction with data from P 24-year cohort study of 1,960 middle-aged employed -. In the total cohort, serum cholesteml was not related to risk of lung cancer. The relative risk associated with a difference of -1 .O mmol per liter in serum cholesterol was 1.01 (95% ccrdidace interval of 0.801.27) after adjustment for cigarette smokiag, age, and intake of beta-carotene. In contrast, however. when tbe study group was restricted to mea with intake of beta-carotene <S,OOO (N = 929) or <3,000 IU per day f,N = 272), comparable relative risks were 1.10 and 1.21. respectively. Although the 95% confidence intervals for these relative risks were broad and included unity, the result is consistent with expectation. We conclude that the hypothesis warrants further investigation.

A tobacm-spedfic N-nitrmomine or [email protected] smoke condemote comes neoplastic transformation of xmotransplanted human broachbdepitbelialc& Klein-Sunto AJP, limsa T. Momiki S. Garcia-PaI= I, Caamano J, Metcalf R et al. Dcpamncnt of Pathology, Far Chase Cancer Cmm, Philadelphia. PA 19111. Pmc Nat1 Acad Sci USA 1992$9:6693-l.

Using * xmotmnsplautation system in which immortalized nonhnmorigenic human bmncbial epitbelial cells (BEAS-2B cells) are g~wnindeepithelializednttnchus~t~subcutmeauslytnnsplsnted into atbymic nude mice, we exposed BEAS-2B cells either to cigarette smoke condensate or to the tobacco-specific N-nitrosamiae 4- (methylnitmsamine)-l- (3-pyridyl)-l-butanone. After 6 ma tbe carcino.getl+.xposed BEAS-2B cells were neotdastically transformed to

in viva to chemicals exhibited several features lypical of t&lignani lung cancer cells. such IS increased in viva invasivemw that wmlated well with enhanced type IV collagenolytic activity, resistance to serum- induced growth inhibition, and increased expression of transforming growth factor 6 and its cellular-membrane receptor. lnvasiveoess, similar to that seen after exposure to phorbol eaten, was also detected after in vitro exposure of BEAS-2B cells to cigarette smoke wndeasate. Collectively, these data indicate that cigzirette smoke condensate and N- nitmsamine4-(metbylnitmsamine)-1<3-pyridyl)-l- butanoneinducein viva phenotypic changes in BEAS-2B cells similar to the progressive changes that occur during human lung carcinogenesis.

in A/J mice by green tea and its major polyphenol as antioxidants Xu Y, Ho C-T, Amin SG, Han C, Cbuag F-L. American Health Founabion, Valhalla, NYIO595. Cancer Res 1992;52:3875-9.

In this study we examined the effects of g- tea and its major components, (-)-epigallocatechin gallate (EGCG) and caffeine, on the tobacco- specific nitmsamine 4-(m&ylnitmaminc+1<3-pyridyl)-I- butanone (NNK)- induced lung hmwrigeoesis in A/J mice. We also studied the effects of green tea and EGCG on @-metbylgunine and 8- hydmxydeoxyguanosine (I-GHdGuo) formation in lung tissues caused by NNK treatma 1. Miceweregiven296 tea, 560ppmEGCG. or 1120 ppm caffeine in drinking water for 13 weeks. During this time, NNK (11.65 mg/kg body weight) was administered by gavage three times weekly for 10 weeks from weeks 3 to 12. The bioassay was (e&ted 6weeksafterthelastNNKtreatment.MicetreatedwithNNKdeveloped 22.5 lung adenomas per mouse. whereas NNK-treated mice that drank green tea or EGCG as drinking w&r developed only 12.2 (P < 0.01) and 16.1 (P C 0.05) htmors per mouse, respectively. Mice that drank greenteaorcnffeine solution showed lowerbody weight gains, although little difference in water and diet consumption was noted in these groups. While green tea and EGCG exerted littleeffect on the formation ofOb-methylguanine,ncriticalDNAlesioninNNKlunghrmorigenesis,

both treatmeats suppressed the increase of I-GH-dGw levels in mouse lung DNA. The inhibition of S-GHdGuo form&m in lung DNA by gneea tea and EGCG is consistent with their ability to inhibit lung tumorigeaesis by NNK. Because S-GHdGuo is a DNA l&m cawed by oxidativedxmage, thesereadtssuggestthat tbemchanismofinhibition by green tea and EGCG in NNK-induced lung htmorigeoesis is due at least partly to their antioxidant properties.

Reevaluation of silii and lung curer in North Carolins dusty tradea workers Amandus H.E. Castellan R.M. Shy C. Heinemxn E.F. Blair A. DRDS/ NIOSH, 944 C?mmuRidge Road. Morpmn. WV2&505-2888. Am I Ind Med 1992;22:147-53.

We previously reported cm the lung cancer mortality tbrougb 1983 of 760 males who were diagnosed with silicosis during 1930-1983 by the State of North Camlii’s medical examination program for dusty trades workers. ThclungcancerSMR (95% confideaceintaval)w2.6 (1.8- 3.6) among 655 white members of this group. In this uwer. w renai

recl&f&l for pneumoconiosis by 3 ‘B’ readen using the &&iLTt) CIassificationLungccerSMRswere 1.7 (O.S-3.1)fortbeentiregmup of 306 whitemales, 2.5 (I. l-4.9) for I43 subjects reclassifiedassimple silicosis, and 1.0 (0.1-3.5) for 96 subjects whose rxdiogmphs were reclassified as IL0 category 0. There were no lung cancer deaths among 67 subjects whose radiographs war. reclassified as progressive massive fibrosis. Corresponding lung canw SMRs for subjects who bad never ~employedinajobwithexposuretolmowoocc~~arcinogens were 1.2(0.2-4.4)fortbosetr&ssitiedascategoryO,and2.4(1.O-5.0) for those re&ssified es having simple silicasis. The age&justed lung c~ncernlerstio~mwgsubjectswithsimplesilicosiscompPred to those with category 0 was 1.5 (0.4-5.8). Our tindings from this reanalysis, which effectively controls for misclassiticptioa of silicasis due to errors in radiograph interpretation by Noatb Carolinx program waders, offer additional evidence consistent with tbe hypothesis of am association between silicosis and lung cancer in this study group.

Compalis6nofltmgmrci-incidarein~ledogsexposedto vuozasyoungadultsorasirmanture~ Griffith WC, Guilmztte ItA, Muggenbwg EA. Inhalation Taricology Rewarch hut., PO Box 58908 Albuquerque, NM 87185. Radial Pmt Dosim 1992;41:101.

Beagle dogs were exposed by inhalation either as immahue ( < 3 months of age) or as young adult (< 13 motttbs of age) dogs to monodispzrsepaticlesof”PuO,. Tbessparticlasan3relativelyinsoluble invivomdtbustbem~jorityofthend~tionQseisdelivmdtotheI~g and associated tissues. As has beea reported previously there - M apparent differences in lung rcteaticm assoc.&d with age at exposure. Timedepeadenl radiation dosm to the lung, averaged over the total lung mass, were calculated to take into account the growing lung of tbe immsturedog.‘Ibercwers108imma~~~s~posedtoammodisperse 1.5 m AMAD +icles (74survivorsxre7-lO years xfterexposwe) and 252 young adult dogs exposed to 0.75, 1.5 or 3.0 m AMAD particles (52 survivors are 1 l-13 years after exposure). To date, 24 immature dogs have died with lung carcinomas at doses of 2.5 to 83 Gy and 104 young adult dogs have died with lung carcinomas xt doses of 3.2 to 89 Gy. The lung carcinoma incidence rates for the hvo study groups were canpa& using a Con pmpcational hazards model with a time- dependentdose. AcommmbPselineincid~centewrc:uscdsothntrisLs would be estimated relative to the same baseline. No statistically significant difference (P > 0.30) was found be@veen the immxtwe and tbe young adult dogs in how their lung cprcinoau incidmce rates bueased with radiation dose. Tbis suggests that there is not *unique mdioseasitivity attributable to a puticle irradiation of x growing lung.

General mortality and respiratory cancer among a cobwt of male chemical workers in California Burchtiel CM, Cartmill JB, Axe FD. Bond Go. Dcponmenr of