© 2001 by Oxford University Press
Journal of the National Cancer Institute, Vol. 93, No. 20, 1511,
October 17, 2001
© 2001 Oxford University Press
IN THIS ISSUE |
-Radiation Sensitivity and Risk of Glioma
-Radiation has been identified as a risk factor for brain tumors. Bondy et al. (p. 1553) further investigated this association by comparing the -radiation sensitivity of lymphocytes from glioma patients and of lymphocytes from matched control subjects. -Radiation sensitivity, a measure of mutagen sensitivity, was assessed by counting the number of chromatid breaks. They found that the frequency of chromatid breaks was higher in glioma patients than in control subjects. They also found that the estimated relative risk for glioma increased with an individual’s sensitivity to -radiation. Consequently, they concluded that -radiation-induced mutagen sensitivity may be associated with an increased risk of glioma.
Dornfeld and Lawrence (p. 1512), in an accompanying editorial, discuss several potential problems with the mutagen sensitivity assay. However, they conclude that an assay, such as the mutagen sensitivity assay, may be a vital first step in measuring the overall DNA repair capacity of an individual.
"Our findings confirm that the sensitivity to -radiation and the subsequent inability to repair radiation-induced DNA damage may increase the risk for brain tumorigenesis."
—Bondy et al.
Night Shift Work, Light at Night, and Risk of Breast Cancer
Exposure to light at night because of night shift work or because of lack of sleep may suppress normal nocturnal production of melatonin by the pineal gland, which in turn could increase the release of estrogen by the ovaries. Davis et al. (p. 1557) in a case–control study and Schernhammer et al. (p. 1563) in a prospective cohort study investigated whether such exposure is associated with an increased risk of breast cancer in women. In spite of different study designs, both research groups conclude that light exposure at night is associated with an elevated breast cancer risk, and this risk increases with increased time of exposure to light due to more hours of work per night and with an increased number of years of work at night.
In an editorial, Hansen (p. 1513) recommends further exploration of the relationship between exposure to light at night, night shift work, and cancers that may be influenced by melatonin.
"Although the possibility exists that work at night or exposure to light at night acts as a proxy for other yet unknown risk factors for breast cancer, ... all of the epidemiologic studies published so far on different indirect measures of light at night and breast cancer risk seem to relatively consistently point to an increased risk."
—Hansen
Zinc Deficiency and Esophageal Cancer in Rats
For rats, a diet that is deficient in zinc increases esophageal cell proliferation and the incidence of N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumors. Replenishing zinc with a zinc-sufficient diet reduces these effects. Fong et al. (p. 1525) investigated whether apoptosis was involved in this reduction of esophageal cell proliferation and tumors. They found that, when zinc was replenished shortly after NMBA treatment, esophageal tumorigenesis was reduced. Twenty-four hours after NMBA treatment, they found numerous apoptotic cells and double the amount of the proapoptotic protein Bax. Within 48 hours, the esophageal epithelium that was 10 to 20 cell layers thick before treatment had decreased to only three to five cell layers thick. Thus, in NMBA-treated zinc-deficient rats, the authors concluded that replenishing zinc rapidly induces apoptosis in esophageal cells and reduces the development of esophageal cancer.
Induction of Cancer in Mismatch Repair-Deficient Mice
The mismatch repair system, which involves a number of genes, carries out surveillance and repair of errors in replication of DNA. Inherited defects in these genes in humans are associated with increased risk of cancer. To better understand the mechanisms by which the mismatch repair system protects against cancer, Colussi et al. (p. 1534) exposed mice deficient in a mismatch repair-related gene, MSH2, to dimethylhydrazine, a carcinogen. They found that mice deficient in both copies of MSH2 succumbed much more quickly to colon tumors following exposure to dimethylhydrazine than mice with one or two functional copies of the gene. They also observed that apoptosis, or programmed cell death, which protects against cancer, only occurred after carcinogen exposure in mice with functional MSH2. The authors conclude that inactivation of MSH2 allows proliferation of damaged gastrointestinal tract cells in mice, which may explain the protective effect of the gene against colorectal cancer.
Effects of Survivin Antagonists on Established Tumor Growth
Overexpression of the inhibitor of apoptosis protein survivin in several common cancers is associated with a poor prognosis. Kanwar et al. (p. 1541) injected tumors derived from thymic lymphoma cells with plasmids encoding antisense survivin and dominant negative mutant survivin, which inhibit survivin expression and function, and the T-cell costimulator, B7-1. The authors found that tumoral survivin expression increased with increasing tumor size and that injection of either survivin-based plasmid inhibited the growth of both small and large tumors, increased levels of intratumoral apoptosis, and stimulated the generation of tumor-specific cytotoxic T lymphocytes (CTLs) compared with tumors injected with empty plasmid. Intratumoral injection with antisense survivin and B7-1 further inhibited the growth of large tumors. The authors conclude that intratumoral injection of plasmids that both block survivin expression or function and stimulate the generation of antitumor CTLs may be beneficial for the treatment of large lymphomas.
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