BIOLOGIC MARKERS IN OCCUPATIONAL AND ENVIRONMENTAL MEDICINE By: Dr Chavoshi

Definition  Any substance, structure, or process that can be measured in the human body or human body products, that may influence or predict disease.

Types of Biomarkers  Biomarker of exposure or internal dose :( BLL, Cadmium in urine).  Biomarker of effects :( measurement of protein or DNA adducts).  Biomarker of susceptibility: demonstrate the possible differences between individuals in metabolism, immune responsiveness, DNA repair mechanisms or alterations of oncogenes and tumor and tumor suppressor genes activities.

Environmental vs biologic monitoring  Environmental monitoring measures the ambient exposure of a chemical through sampling of the air or surfaces at the workplace.  Acute exposures to chemicals, to evaluate engineering control measures, to prevent overexposure and to provide a more accurate monitoring of chemicals.

Selection of Biomarkers  Rout of exposure  Respiration rate  Metabolic and excretion rate  Genetic  Adipose tissue level

Biomarkers Exposure Internal dose Biologically effective dose Early biological effect Altered structure/ function Host factors(susceptibility) Clinical disease GenotypeEnvironment Biomarker ofBiomarker of susceptibility Early biological effect

Biomarker of exposure  Exposure measurement to chemical independent of rout of exposure.  Reflection of the amount of the chemical in question or its metabolite present in the biologic sample.  Direct measurement: urine, blood, exhaled air, feces, hair, nails, saliva, breast feeding  Examples: s-phenylmercapuric acid for benzen exposure, neutron activation for cadmium exposure

Characteristic of useful biomarkers of exposure  Correlation with exposure  Correlation with target tissue dose  Appearance is reversible  Influence of confounding and modifying factors is well characterized.  Suitable for application in the workplace

Biomarker of effect  Measure reversible biochemical changes that occure after receipt of an internal dose.  These markers may predict adverse effects.  They must be distinguished from tests that true pathological effects.  Examples: measurement of protein or DNA adduct burden for aromatic amine exposure.

Biomarker of susceptibility  Demonstrate the possible differences between individuals in metabolism, DNA repair, immune responsiveness, or alterations of oncogenes and tumor suppressor genes activities.  Measurement with using modern molecular biologic techniques, including the PCR, the polymorphisms, or genetic differences.  This type of biomarker is used for prevention of possible exposure risk.  Example: use of genetic testing for susceptibility to beryllium exposure.

Criteria for choosing and implementing a biomarker  Determinate must be present in an available biologic medium and suitable for sampling.  The sampling method must be convenient and acceptable to tested population.  The sampling method must produce representative and useful samples for analysis  Analysis method must be practical, accurate, and reproducible.  Responding to aberrant results.

Sampling  For accurate monitoring of exposures, the timing and appropriateness of sampling must be considered for each type of exposure.  Sampling during or at the end of a working shift for chemicals that are rapidly cleared from the body may require more immediate sampling.  Collection method may be important for accurate analysis  Selection of appropriate preservatives.  Baseline testing : For chemicals that accumulate in the body or for substantial inter individual variability. ( cadmium, lead, PCB).

Samples type  Blood: little variability between individuals and no need for correction for individual differences.  Urine: detection of various hydrophilic chemicals, metals, and metabolites.  A 24- hour urine collection is an accurate assessment  Urine sampling is not appropriate for advanced renal disease.  Exhaled air: useful for volatile chemicals, and no useful for aerosols, gases, vapors that decompose upon contact with body tissue or highly water soluble. Exhaled air sampling is not done in workers with emphysema.

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