This research assessed differences in DNA repair in lymphocytes from highand low-distressed individuals. A median split on Minnesota Multiphasic Personality Inventory (MMPI) Scale 2 divided 28 newly admitted nonpsychotic psychiatric inpatients into high-and low-distress subgroups.The high-distress subgroup had significantly poorer DNA repair in lymphocytes exposed to X-irradiation than low-distress subjects. We also found that lymphocytes obtained from this psychiatric sample had significantly poorer DATA repair than lymphocytes from nonpsychiatric control subjects when compared 5 hr after X-irradiation. A high level of distress therefore appears to be associated with significant dysfunctional differences at the molecular level which may have important implications for health. These data provide evidence for a direct pathway through which distress could influence the incidence of cancer.

No abstract

Pathologic response of tissue to asbestos in vivo gives rise to fibromatoma, granuloma and mesothelioma. We are attempting to develop a model system in vitro using human cells in order to investigate the possible mechanisms responsible for these pathologies.Within the first 12 hr of exposure to chrysotile, the fibroblasts showed distinctive morphological changes. Cells appeared elongated with occasional vacuolated nuclei and granular cytoplasm. Cells showed no other obvious morphological changes by light microscopy and were serially passaged at confluence. The cells with vacuolated nuclei were successfully serially passaged. Binucleated cells were first observed 48 hr after passaging. As time in culture increased (3 days to 2 weeks) many cells lost their distinctive bipolar properties and developed "stress striations" and multiple vacuoles in the cytoplasm. Multinucleated giant cells (2-11 nuclei/cell) with lobate nucleoli became more numerous. With increasing passages, the confluent cell density decreased and cell size increased. Cells usually had condensed nucleoli and had lost all control of directional growth. Preliminary indications suggest that these in vitro morphological transformations are due-at least in part-to a lack of control over cytokinesis.

No abstract

The risk of lung cancer related to asbestos exposure has been shown to increase disproportionately by cigarette smoking, suggesting a synergistic effect. Differing lengths of NIEHS chrysotile with benzopyrene [B(a)P, B(e)P] (organic by-products of combustion) were applied on normal human fibroblasts (cell line Cl) to test for cytotoxicity (survival determined by colony-forming efficiency), binding of benzopyrene to DNA, and the production of benzopyrene metabolites.At concentrations of 100 pg/mL, NIEHS short chrysotile was more cytotoxic than NIEHS intermediate chrysotile (3% and 17% survival, respectively), B(a)P and B(e)P concentrations up to and including 10pM were not cytotoxic. Simultaneous application of NIEHS short chrysotile with B(a)P or B(e)P did not decrease survival synergistically. On the contrary, application of B(a)P simultaneously with NIEHS intermediate chrysotile resulted in increased survival over that of intermediate chrysotile alone (25% and 17% survival, respectively). There were low levels of B(a)P bound to DNA in the presence of NIEHS short chrysotile or NIEHS intermediate chrysotile. Measurable levels of B(a)P-DNA adducts were formed both in the absence and in the presence of each size of NIEHS chrysotile. However, there was no strong indication of a perturbation of the level of DNA-B(a)P binding following simultaneous administration of increasing levels of asbestos in addition to 1 JM hydrocarbon. The asbestos had no demonstrable influence on the level of B(a)P metabolism during the 24-hr period following simultaneous exposure of asbestos and hyrdocarbons. In addition, the B(a)P-deoxynucleoside adducts formed both in the presence of 1 mgdmL short chrysotile and in its absence, as determined by co-chromatography on HPLC with standards formed by the reaction of the (+ )anti-benzo(a)pyrenediol epoxide at the exocyclic amino group of deoxyriboguanosine (NI).

tients, families, and scientists, public health researchers and other investigators must reconsider their methods of doing research and obtaining consent before publication of results. The risk to public health caused by a loss of trust in the scientific community is surely one of the greatest plagues we face.