Health Effects of Environmental Agents
Health Effects of Environmental Agents ENVR 430
Popular in Course
Popular in Environment
This 8 page Class Notes was uploaded by Thelma Dickens on Sunday October 25, 2015. The Class Notes belongs to ENVR 430 at University of North Carolina - Chapel Hill taught by Louise Ball in Fall. Since its upload, it has received 24 views. For similar materials see /class/228860/envr-430-university-of-north-carolina-chapel-hill in Environment at University of North Carolina - Chapel Hill.
Reviews for Health Effects of Environmental Agents
Report this Material
What is Karma?
Karma is the currency of StudySoup.
Date Created: 10/25/15
ENVR 430 Wednesday October 4 2006 CANCE R A maausal mulrslage group ofdrseases me mechanisms ofwmcn are am only partially known l ARC Scientific Publications 1992 quotCancer abnormaces mar can reSul in death Arnencan Cancer Society 2006 Chemical Carcinogenesis Initiation Promotion Progression Age adjusted Cancer Death Rates by Site Us 19302002 a oramry of Environmental Genomics Department of Environmental Sciences amp Engineering Hrmc edu 84372596 0031 Nil RC WHAT MAY CAUSE CANCER gt Hereditary disorders gt Chemicals gt Viruses gt Chronic in ammation gt o Benign tissue is not canoer Although the cell growth is moderately increased the cells do not invade nearby tissue or spread to other pans of the body 0 Malignant tissue is cancer The cancer cells divide out of 39quot39 quot quotiquotquot Hm 39quotI E quotiquot 39 quot control They can invade and destroy nearby healthy tissue Also cancer cells can break away from the tumor they form and enter the bloodstrmm and lymphatic system Affeued o Metastasis the spread of canoer beyond the organ of origin me h plwwwcnmzrsuppnmcm camriskmlm Mm History of Chemical Carcinogenesis History Of Chemical carCinogeneSiS Large numbers of chemicals were tested for carcinogenic potential in the 19701990s Maximum Tolerated Doses MTD were used 60 of rodent carcinogens were genotoxic 40 of rodent carcinogens were nongenotoxic Chemical carcinogenesis was first suggested by clinicians 200 years ago Scrotal cancer in chimney sweeps Potts Nasal cancer and snuff dipping Hi Today gt50 chemicals are recognized as Some chemicals were single site single species human carcinogens carcinogens Others were multisite multispecies carcinogens 0 First experimental studies in animals Doseresponse varies from lt12 MTD to lt11000 MTD were done 80 years ago Most regulations use straight mathematical extrapolation of high dose rodent data to predict risks IARC 2004 Carcinogenic to humans group 1 Probably carcinogenic to humans group 2A Possibly carcinogenic to humans group 28 Not classi able as to its carcinogenicity to humans group 3 Probably not carcinogenic to humans group 4 US EPA 2003 Carcinogenic to humans Likely to be carcinogenic to humans Suggestive evidence of carcinogenic potential nadequate information to assess carcinogenic potential Not likely to be carcinogenic to humans 7 international Agency far Research on Cancer iARC Centre lntemational de Recherche sur le Cancer CIRC Volumes 1 inroug oBius Suppiumaulr 7 US NTP 2002 Known to be a human carcinogen Reasonably anticipated to be a human carcinogen CalEPA 2004 Known to the state to cause cancer MRC l5 Cmn Ailwu Thomas 5917 l ymi Fl39iFX 0R Fianro 0 mm Tel31n l7 71 TH RS 7 fax 711014 77 7121 7quot Dg anug 3 IMPOUNDS evldence Cancer Cases Attributable to Environmental Carcinogens Worldwide 1990 Infections viruses parasites H pylori 16 Tobacco smoked and smokeless 14 Occupation 4 Alcohol drinking 3 37 Diet and dietary components including contaminants 25 Pollution 2 Reproductive factors 2 29 IARC Group 1 Carcinogenic to humans Monographs Volumes 184 19722002 89 Agents and Exposures Medical drugs and treatments 24 Industrial processes 1 3 Infectious agents or processes 1 0 Physical agents 1 0 Industrial chemicals 7 Inhaled particulates 5 Metals and inorganic salts 5 Lifestyle factors incl herbal remedies 7 Other 8 Exposures to Chemicals in the Workplace Proved Excess Cancers and bronchus Mudl ed 39um Cullen at al 19 Carcinogenic Risks of Chemical Agents Associated with Medical Therapy and Diagnosis Carcinogenic Factors Associated with Lifestyle Pranmopausal Mum ed inth 1m and Vamm 21210991 Chemical Carcinogenesis Stages Of Gummyenes39s Initiation In the 21 st Century Olnitiatinga Cell Proliferation gt gt gt gt gt New perceptions of previously known carcinogens Event 39 quota39 expan s lgquot l a Combined effects of multiple exposures 5W Promotion Examples 0 Alcohol drinking and a atoxins 0 Alcohol drinking and HBVIHBC 0 Alcohol drinking and tobacco smoking 0 Alcohol drinking and asbestosarseniclradon Progression Cell Proliferation 39 Malignancy Cellular and Molecular Mechanisms in Multistage Carcinogenesis INITIATION Initiating event involves cellular genome MUTATIONS oncogenestumor suppressor genes signal transduction ce cycleapoptosis regulators Target genes Simple genetic changes W 8 83 3 Repelitlon Deletion me http newszentei cancer govscienzebehmd ENDOGENOUS DNA DAMAGE SOURCES OF MUTATIONS EXOGENOUS DNA DAMAGE Free Polymerase Environmental Life Radicals Errors Depurination Agents Styles DNA REPAIR l l l l l I CELL REPLICATION V MUTATION Chemical Exposure air water food etc Internal Exposure Metabolic Activation Macromolecular Binding Detoxication 1 DNA Protein 1 RNA Biomarker Biologically Effective Dose X Efficiency of Mispairing Initiation X Cell Proliferation Possible pathways of activation ofsuspcctcd humnii carcinogens NH N iieiemcyciic mines an IQ l lill Amman amim c g min I Alls g amp DMBA N 7cm DNAnuclch lmdurlsul metabolic Icti mion V CH1 Yrq 39il 39 s N W 1m 5 p lln f 0301 E T pma HIVOH 1 Nquot N N g 3117 HNfOCH 39 Phll 30 39Irgt Aha H 0 C39 lABP q KO 539 V cw any Su v 1 Digjdaz ml i nil1 57 m a P07 running HlRCLOH N a c 39 LYI IRTV HT A mismxx 39r V m iDihdro39xy Tetra Llcclmpliile metabolite 3le Williams JA Carcinogenesis 22 209714 2001 Accumulation of mutations during tumor progression gltlltlt 1 Environmental Endogenous DNA repair mm 7 selection to Selection for DNA mm 9 Mutalions Mahms mum amp ma quotam 9 mutate genes 9 mutators pnenoiype l l 20 years Clinical detection LoebLA CancerRes 61 323079 2001 Cellular and Molecular Mechanisms in Multistage Carcinogenesis PROMOTION Reversible enhancementrepression of gene expression increased cell proliferation inhibition of apoptosis No direct structural alteration in DNA by agent or its metabolites SUVmen sumuiaiion o J o N ole s r 7 509 0 6 f quot 0 mm on mm Iy swam proteins Change incall behavior 39 a l5 9 Increased promeraivon lncreased mummy From http Unewscenter cancer govsciencebehmd Role of Increased Cell Proliferation in Carcinogenesis Decreases time available for DNA repair Converts repairable DNA damage into nonrepairable mutations not DNA damage anymore Necessary for chromosomal aberrations insertions deletions and gene amplification CIonaIIy expands existing cell populations with mutations 139 X gt No Tumors 2 x 1 l I I 1 1 I I Tumors 3 X LLLLLLLV Tumors 4 LLLLLLLLLX No Tumors 5 LLLLLLLLY No Tumors Time gt X Application of Initiator V Application of Promoter Cellular and Molecular Mechanisms in Multistage Carcinogenesis PROGRESSION o Irreversible enhancementrepression of gene expression N Basophmc Focus Ad mmt 0 Complex genetic alterations chromosomal translocations deletions gene amplifications recombinations etc o xk o Progression o o o Q 0 Selection of neoplastic cells for optimal growth genotype phenotype in response to the cellular environment u g 1 7 LE HHHHHHHHH N Tum rs E Mismatch Deletion HVVVVVVVVVVVYVVYVVVVVVVVVVVVVVVY E Tumors Complex V Application of Promoter genetic a changes Adapted from Marsman and Popp Carcinogenesis 15111117 1994 Repetition Deletion E Human Tumors and Stages of Carcinogenesis Phenotypic characteristics of cancer cells Defects in Terminal Diiierentiation S Defects in Growth Control unxo Immortazat0n M Resistance to Cytotoxicity i 0 Transformation g w I him 153 K9 am 222 0 Loss of contact growth inhibition A 2 77 035 lt I 3 9a o Autonomy of proliferation g N ORMAL CELL INITIATED PRENEOPLAS HC MALIGNANY CLINICAL CLINICAL I I v CELL LESION TUMO CANCER CANCER o Avondance of apoptosns Ft1 Aberrant differentiation g o Activation of ProtoOncogenes inactivation ol Tumor Suppressor Genes t Inactivation of Antimetastasis Genes Histopafhological and molecular events leading to esophageal adenocarcinogenesis Multiple Stages of Human Colon Cancer W a mumm 7uwnlm quot 1 mm in Mi 7 km III 1M 32 um t mm a 1 n Unrume M a mum Cnlumnuplimd CL wilh Esophagul Normal 5 mrinnd gt nphngilli gt Empllnxur gt Dysylmm gt1dmmrrlmma MCll duodmml iGERD 1cm Em DNA m1 mm mnttnu lnqeued G39wp 39 CIIGM 6 MW hmmi lmselDCCGeM l mu mum mmmnnmlxllvumnel mm unm mkcmw O le MWMWWH n lk gmemvumlamluy llIncrpmhlcmnun N a I melpsmem wincxnl mun mmpmupmunmucmmm quot1quot 31mm 5 ammugmmmmpmt gt mummmvHm shimmy umv enzymes mm mm was Rnulvevnamswits W mum DNAsmdawm mm mm Marx 1917 um WWW Chen and Yang Carcinngmesas 2211192wm1 pm mp WW cmcqmmm cam WWW Genetic changes underlying development and Stages of Carcinogenesis progression of prostate cancer I T f nl la an Init ting Cell Proliferation Q g Event Tzlonal expansion quot53quot Wang MM if tiiz id39 1 Promotion quot39m39i39zl W n mm Progressmn avng Cell Proliferation gt Malignancy