Other highlights in the December 1 JNCI

A new study of pesticide applicators has found that exposure to the pesticide chlorpyrifos may be associated with an increased incidence of lung cancer but concludes that more studies are needed.

About 8 to 10 million pounds of the insecticide chlorpyrifos were used in the U.S. agricultural sector in 1999. The chemical is found in approximately 800 products, which are used for a variety of purposes, including pest control of food crops, indoor pest control, and pet collars. Chlorpyrifos was widely used in U.S. households until 2000, when the Environmental Protection Agency phased out or limited some residential uses. Although there was little previous epidemiologic evidence of an association between exposure to chlorpyrifos and human cancer, human and animal studies have provided evidence that the chemical may be able to damage DNA.

To evaluate the incidence of cancer among pesticide workers exposed to chlorpyrifos, Michael C. R. Alavanja, Dr.P.H., of the National Cancer Institute, and colleagues analyzed data from the Agricultural Health Study, a prospective cohort study of more than 54,000 pesticide applicators from Iowa and North Carolina. For all cancers combined and for most cancers analyzed, they found no evidence of a relationship with exposure to chlorpyrifos. However, increased chlorpyrifos exposure was associated with an increased incidence of lung cancer. Individuals in the highest quartile of lifetime exposure-days had more than twice the risk of lung cancer compared with those with no chlorpyrifos exposure. The authors note that this result was not anticipated and that the lung cancer association should be interpreted cautiously until it is confirmed in future follow-ups of the AHS cohort and other studies.

Contact: National Cancer Institute Press Office, 301-496-6641, NCIPressOfficers@mail.nih.gov

Study Investigates Celocoxib-Induced Apoptosis in Human Lung Cancer Cells

Celecoxib (Celebrex), a COX-2 inhibitor, can induce apoptosis, or "programmed cell death", in various cancer cell lines through a mechanism that is independent of its COX-2 inhibitor activity but is otherwise uncharacterized. In a new study, Shi-Yong Sun, Ph.D., of the Winship Cancer Institute in Atlanta, and colleagues investigated the mechanism of celecoxib-induced apoptosis in human non-small cell lung carcinoma (NSCLC) cell lines.

They found that treatment with celecoxib decreased cell survival, activated caspase (mediators of apoptosis) cascades, and increased DNA fragmentation by a pathway involving death receptor induction and caspase-8 activation. The authors conclude that celecoxib appears to induce apoptosis in human NSCLC cells through the extrinsic death receptor pathway.

Contact: Vincent Dollard, Communications, Winship Cancer Institute, 404-778-4580, vincent_dollard@emoryhealthcare.org

Study Examines Proteins' Relation to DNA Repair and Malignant Melanoma

A reduced capacity to repair UV-induced DNA damage has been associated with an increased risk of cutaneous malignant melanoma, but the molecular mechanism of the association is not known. The INK4a/ARF locus, which contains two known tumor suppressors, is often mutated in melanomas and in the cells of patients with familial malignant melanoma, but it is not known if the locus is involved in DNA repair.

In a new study, Thomas M. Rünger, M.D., of the Boston University School of Medicine, and colleagues measured and compared DNA repair in cells from normal mice and cells from mice with one or both of the tumor suppressors mutated. The mutant cells had a lower capacity for DNA repair compared with the normal cells. The authors conclude that mutation of the INK4a/ARF locus may predispose people to melanoma because of a reduced ability to repair sun-induced DNA damage in addition to the loss of tumor suppressor function.

Contact: Thomas M. Rünger, Boston University School of Medicine, 617-638-5551, truenger@bu.edu

Also in the December 1 JNCI: