DNA Adducts in Human Tissues: Biomarkers of Exposure to Carcinogens in Tobacco Smoke

Abstract

453-458 (1996)

Carcinomas of the renal pelvis associated with smoking and phenacetin abuse:p53 mutations and polymorphism of carcinogen-metabolising enzymes

“…p53 mutations were significantly more frequent in invasive than in non-invasive cancer ( p Ͻ 0.001) and in tumours with grades 3 or 4 than in those with grades 1 or 2 ( p Ͻ 0.05). (Phillips, 1996). Double p53 mutations have been found frequently in bladder cancer in smokers Kusser et al, 1994), whilst in the present study, there was no correlation between the presence of double mutations and smoking history (Table I).…”

Biomonitoring of tobacco smoke carcinogenicity by dosimetry of DNA adducts and genotyping and phenotyping of biotransformational enzymes: a review on polycyclic aromatic hydrocarbons

“…The latter have been used mainly in studies where the population under investigation consists of healthy individuals. Conceivably, most target organs for smoking-related cancers are not readily obtainable and require surgical or somewhat invasive procedures, precluding, for practical or ethical reasons, widespread population sampling or repeated sampling of the same individual (Phillips 1996).…”

“…In 32 P-postlabelling analyses, smokers show a typical diagonal radioactive zone (DRZ) generated by the resolution of labelled 1-OH 3-OH 6-OH 7-OH 9-OH Quinones 1,6 3,6 6,12 9-OH-4,5-oxide DN A adducts 9-OH-4,5-diol DNA digests on two-dimensional thin-layer chromatograms. This is widely regarded as an indication of the formation of a complex mixture of adducts in the respiratory tract as a result of exposure to tobacco smoke (Phillips 1996). More recently, ammonium hydroxide-based thin layer chromatography solvents have been introduced, which resolve adduct DRZ into discrete spots and allow determination of adducts derived from various classes of compounds, including PAHs (Spencer-Beach et al 1996).…”

Genotoxicity: damage to DNA and its consequences

“…Many different tissues have provided DNA for such studies [85], including blood, sputum, buccal mucosa, cervical mucosa, sperm, bladder (exfoliated urothelial cells in urine), placenta and hair roots. DNA from these accessible sources of human cells have been used in many studies, but by far the most commonly used tissue source has been blood cells (either lymphocytes or the whole fraction of nucleated white blood cells).…”