Inflammation, chromosomal instability, and cancer: the schistosomiasis model.
Evidence is accumulating in support of a role for reactive oxygen species in the etiology of cancer. Inflammatory cells, such as neutrophils, macrophages, and eosinophils, are an important endogenous source of oxygen radicals. Stimulation of these cells by tumor promoters or by foreign bodies (parasites, bacteria, etc.) causes the release of reactive oxygen species. Laboratory studies have shown that genetic damage and neoplastic transformation are induced in vitro in cells cocultured with activated inflammatory cells. We have recently begun to study the role of inflammatory reactions in inducing genetic damage in a human population. This paper describes our initial studies of Egyptian patients infected with Schistosoma haematobium. This infection induces chronic inflammation and irritation in the urinary bladder and is associated with increased cancer at this site. We describe a recently completed population study that shows that infected individuals have elevated levels of genetic damage in their bladders, as measured by the exfoliated cell micronucleus test. Treatment that kills the parasite also reduces the micronucleus frequencies. We also explore the hypothesis that altered sensitivity of clones of cells in these patients to reactive oxygen species could be a force that drives the development of neoplasia by facilitating clonal expansion. Evidence is presented for the possible involvement of loci on chromosome 11 in controlling the level of chromosomal breakage caused by oxidative damage. We have shown that bladder carcinoma cells are sensitive to micronucleus induction by promoter-activated neutrophils and that they can be protected from this damage by insertion of a normal chromosome 11. Further work is in progress to define the source of chromosomal breakage in schistosomiasis patients and to begin to develop an understanding of the host factors protecting bladder cells in these individuals from genetic damage.
Rosin
M P
MP
Epidemiology Division, British Columbia Cancer Agency, Vancover, Canada.
Anwar
W A
WA
Ward
A J
AJ
D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D006801:Humans; D007249:Inflammation; D015162:Micronucleus Tests; D008954:Models, Biological; D009369:Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D012307:Risk Factors; D012552:Schistosomiasis / Q000150:complications / Q000503:physiopathology*; D012553:Schistosomiasis haematobia / Q000150:complications / Q000503:physiopathology*; D001743:Urinary Bladder / Q000473:pathology*; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology* / Q000235:genetics