Biomonitoring human exposure to environmental carcinogenic chemicals.
A coordinated study was carried out on the development, evaluation and application of biomonitoring procedures for populations exposed to environmental genotoxic pollutants. The procedures used involved both direct measurement of DNA or protein damage (adducts) and assessment of second biological effects (mutation and cytogenetic damage). Adduct detection at the level of DNA or protein (haemoglobin) was carried out by 32P-postlabelling, immunochemical, HPLC or mass spectrometric methods. Urinary excretion products resulting from DNA damage were also estimated (immunochemical assay, mass spectrometry). The measurement of adducts was focused on those from genotoxicants that result from petrochemical combustion or processing, e.g. low-molecular-weight alkylating agents, PAHs and compounds that cause oxidative DNA damage. Cytogenetic analysis of lymphocytes was undertaken (micronuclei, chromosome aberrations and sister chromatid exchanges) and mutation frequency was estimated at a number of loci including the hprt gene and genes involving in cancer development. Blood and urine samples from individuals exposed to urban pollution were collected. Populations exposed through occupational or medical sources to larger amounts of some of the genotoxic compounds present in the environmental samples were used as positive controls for the environmentally exposed population. Samples from rural areas were used as negative controls. The project has led to new, more sensitive and more selective approaches for detecting carcinogen-induced damage to DNA and proteins, and subsequent biological effects. These methods were validated with the occupational exposures, which showed evidence of DNA and/or protein and/or chromosome damage in workers in a coke oven plant, garage workers exposed to diesel exhaust and workers exposed to ethylene oxide in a sterilization plant. Dose reponse and adduct repair were studied for methylated adducts in patients treated with methylating cytostatic drugs. The biomonitoring methods have also demonstrated their potential for detecting environmental exposure to genotoxic compounds in nine groups of non-smoking individuals, 32P-postlabelling of DNA adducts being shown to have the greatest sensitivity.
Farmer
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PB
MRC Toxicology Unit, Hodgkin Building, Leicester University, PO Box 138, Lancaster Road, Leicester LE1 9HN, UK.
Sepai
O
O
Lawrence
R
R
Autrup
H
H
Sabro Nielsen
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P
Vestergård
A B
AB
Waters
R
R
Leuratti
C
C
Jones
N J
NJ
Stone
J
J
Baan
R A
RA
van Delft
J H
JH
Steenwinkel
M J
MJ
Kyrtopoulos
S A
SA
Souliotis
V L
VL
Theodorakopoulos
N
N
Bacalis
N C
NC
Natarajan
A T
AT
Tates
A D
AD
Haugen
A
A
Andreassen
A
A
Ovrebø
S
S
Shuker
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DE
Amaning
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KS
Castelain
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P
D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity; D001798:Blood Proteins / Q000187:drug effects; D002274:Carcinogens, Environmental / Q000633:toxicity*; D016022:Case-Control Studies; D018736:DNA Adducts / Q000097:blood; D004249:DNA Damage; D004781:Environmental Exposure; D004784:Environmental Monitoring / Q000379:methods*; D004811:Epichlorohydrin / Q000633:toxicity; D005027:Ethylene Oxide / Q000633:toxicity; D006801:Humans; D008752:Methylene Chloride / Q000633:toxicity; D009153:Mutagens / Q000633:toxicity; D009589:Nitrogen Oxides / Q000633:toxicity; D016273:Occupational Exposure; D010578:Petroleum / Q000633:toxicity; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity; D020058:Styrene; D013343:Styrenes / Q000633:toxicity
D018906:Antineoplastic Agents, Alkylating; D001798:Blood Proteins; D002274:Carcinogens, Environmental; D018736:DNA Adducts; D009153:Mutagens; D009589:Nitrogen Oxides; D010578:Petroleum; D011084:Polycyclic Aromatic Hydrocarbons; D013343:Styrenes; D004811:Epichlorohydrin; D020058:Styrene; D008752:Methylene Chloride; D005027:Ethylene Oxide