- Email: [email protected]
Reevaluation of silicosis and lung cancer in North Carolina dusty trades workers
124
Abstracts/Lung
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.
Epidemiology 1992$:282-l. This paper bypothe.sixesthat 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
A tobacm-spedfic N-nitrmomineor [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 nonhnmorigenichuman 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+.xposedBEAS-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 seruminduced 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 indicatethatcigzirettesmoke condensateand Nnitmsamine4-(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.
of gtea and its major components, (-)-epigallocatechingallate (EGCG) and caffeine, on the tobacco- specific nitmsamine 4-(m&ylnitmaminc+1<3-pyridyl)-Ibutanone (NNK)- induced lung hmwrigeoesis in A/J mice. We also studied the effects of green tea and EGCG on @-metbylgunine and 8hydmxydeoxyguanosine (I-GHdGuo) formationin 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, In this study we examined the effects
Cancer 10 (1993)
123-150
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. HeinemxnE.F. Blair A. DRDS/ NIOSH,
944 C?mmuRidge
Road. Morpmn.
WV2&505-2888.
Am
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 medicalexaminationprogram fordusty trades workers. ThclungcancerSMR (95% confideaceintaval)w2.6 (1.83.6) among 655 white membersof this group. In this uwer. w renai I
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 to those c~ncernlerstio~mwgsubjectswithsimplesilicosiscompPred with category 0 was 1.5 (0.4-5.8). Our tindings from this reanalysis, which effectively controls for misclassiticptioaof silicasis due to errors in radiograph interpretationby 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 rcteaticmassoc.&d with age at exposure. Timedepeadenl radiationdosm 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 timedependentdose. AcommmbPselineincid~centewrc:uscdsothntrisLs would be estimated relative to the same baseline. No statistically significant difference (P > 0.30) was found be@veenthe 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 attributableto a puticle irradiationof 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
Abstracts/Lung
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.
Epidemiology 1992$:282-l. This paper bypothe.sixesthat 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
A tobacm-spedfic N-nitrmomineor [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 nonhnmorigenichuman 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+.xposedBEAS-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 seruminduced 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 indicatethatcigzirettesmoke condensateand Nnitmsamine4-(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.
of gtea and its major components, (-)-epigallocatechingallate (EGCG) and caffeine, on the tobacco- specific nitmsamine 4-(m&ylnitmaminc+1<3-pyridyl)-Ibutanone (NNK)- induced lung hmwrigeoesis in A/J mice. We also studied the effects of green tea and EGCG on @-metbylgunine and 8hydmxydeoxyguanosine (I-GHdGuo) formationin 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, In this study we examined the effects
Cancer 10 (1993)
123-150
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. HeinemxnE.F. Blair A. DRDS/ NIOSH,
944 C?mmuRidge
Road. Morpmn.
WV2&505-2888.
Am
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 medicalexaminationprogram fordusty trades workers. ThclungcancerSMR (95% confideaceintaval)w2.6 (1.83.6) among 655 white membersof this group. In this uwer. w renai I
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 to those c~ncernlerstio~mwgsubjectswithsimplesilicosiscompPred with category 0 was 1.5 (0.4-5.8). Our tindings from this reanalysis, which effectively controls for misclassiticptioaof silicasis due to errors in radiograph interpretationby 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 rcteaticmassoc.&d with age at exposure. Timedepeadenl radiationdosm 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 timedependentdose. AcommmbPselineincid~centewrc:uscdsothntrisLs would be estimated relative to the same baseline. No statistically significant difference (P > 0.30) was found be@veenthe 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 attributableto a puticle irradiationof 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