Module 3: Toxicology - Section 13: Occupational Carcinogenesis
TOX 13.13: Carcinogen Exposure Assessment

CARCINOGEN EXPOSURE/BIOLOGICAL EFFECT ASSESSMENT:

Measurements of DNA and protein adducts have been conducted in laboratories. These are essentially sensitive and specific assays detecting minute amounts of adducts. Assay methods include nucleotide chromatography, immunoassays, flourescence spectroscopy, and gas chromatography-mass spectroscopy.

For example:

  1. Exposures to PAH compounds from occupational, habitual and other sources are associated with  increased adduct levels. In the case of occupational exposures levels have been found to decrease during vacations.
     
  2. Endogenous nitrosamines can be estimated by administration of proline resulting in the formation of nitrosoproline which is excreted in the urine, and  is associated with increased risk for stomach and oesaphageal cancer. Nitrosamine adducts can also be measured directly and their presence is associated with increased cancer incidence.  Dosimetry has generally focussed on haemoglobin nitrosamine adducts rather than DNA adducts.  Levels of these Hb-adducts decrease with removal from exposure. Adducts have been correlated with exposure to tobacco exposure using phosphorous 32 postlabelling assays in human lung and placenta. Nitrosamines from tobacco smoke are potent carcinogens in lab animals, with levels higher in secondary than in mainstream smoke. This raises concern for passive exposure to tobacco smoke.

 

Interactive Effects of Carcinogen Exposure and Host Factors:

Interactive effects of chemical and viral agents, chemical and physical agents and host factors have been observed.

  1. Aflatoxin B and hepatitis viruses leading to hepatocellular carcinoma especially with the consumption of alcohol
  2. Tobacco smoke and radon exposure in uranium miners increases lung cancer
  3. Asbestos and tobacco smoke resulting in bronchogenic carcinoma.
Table 1: Interactive Effects of Carcinogen Exposure
Type Example Associated tumour
Chemical-chemical tobacco smoke + alcohol otolaryngeal, oesaphageal
Viral-chemical HPV + tobacco smoke cervical
EBV + nitrosamine nasopharyngeal
HBV + aflatoxin B liver
Physical-chemical asbestos + tobacco smoke lung
radon + tobacco smoke lung
Chemical-host PAH + cyto P4130  CYP2D6 enzyme lung
tobacco smoke + P4130 CYP2D6 lung
chemotherapy leukaemia
Physical-host asbestos + P4130 CYP2D6 lung
sunlight + xeroderma pigmentosa skin
radiation + retinoblastoma deficient genotype osteosarcoma
Viral-host EBV + X-linked immunodeficiency syndrome lymphoma



Creative Commons License
Postgraduate Diploma in Occupational Health (DOH) - Modules 3: Occupational Medicine & Toxicology (Basic) by Profs Mohamed Jeebhay and Rodney Ehrlich, Health Sciences UCT is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 2.5 South Africa License. Major contributors: Mohamed Jeebhay, Rodney Ehrlich, Jonny Myers, Leslie London, Sophie Kisting, Rajen Naidoo, Saloshni Naidoo. Source available from here. For any updates to the material, or more permissions beyond the scope of this license, please email healthoer@uct.ac.za or visit www.healthedu.uct.ac.za. Last updated Jan 2007.
Disclaimer note: Some resources and descriptions may be out-dated. For suggested updates and feedback, please contact healthoer@uct.ac.za.