Skin cancer and chromosomal aberrations induced by ultraviolet radiation. Evidence for lack of correlation in xeroderma pigmentosum variant and group E patients.

Ultraviolet radiation (UV) in sunlight induces an abnormally high incidence of skin cancer in patients with xeroderma pigmentosum (XP), an autosomal recessive disease with defects in the repair of damaged DNA. We determined the frequency of UV-induced chromosomal aberrations in cultured lymphoblast lines from a patient with the variant form of XP, from a patient with the complementation group E form, and from two patients with the complementation group C form. In contrast to results with patients having other forms of XP, the group E and variant patients showed no abnormal increase in UV-induced chromosomal aberrations. Even in the presence of caffeine, which exacerbates the postreplication repair defect of UV-irradiated XP variant cells, there was still no abnormally elevated frequency of UV-induced chromosomal aberrations in the variant cells. These results, indicating that the level of UV-induced chromosomal aberrations is not correlated with these patients' marked susceptibility to skin cancer, suggests that some mechanism other than genetic transposition is causatively related to these XP patients' high incidence of sunlight-induced skin cancer.

Ultraviolet light-induced chromosomal aberrations in cultured cells from Cockayne syndrome and complementation group C xeroderma pigmentosum patients: lack of correlation with cancer susceptibility.

Both Cockayne syndrome (CS) and xeroderma pigmentosum (XP) are inherited diseases with defective repair of damage induced in DNA by UV. Patients with XP, but not those with CS, have an increased susceptibility to formation of sunlight-induced skin tumors. We determined the frequency of UV-induced chromosomal aberrations in cultured lymphoblastoid cell lines from five CS patients and three complementation-group-C XP patients to determine whether such aberrations were abnormally increased only in the XP cells. We found that CS cells had the same abnormally increased number of induced aberrations as the XP cells, indicating that the number of UV-induced aberrations in XP group C cells does not account for the susceptibility of these XP patients to sunlight-induced skin cancer.

Hypersensitivity to ionizing radiation in cultured cells from Down syndrome patients.

Down syndrome is caused by trisomy of chromosome 21 and is comprised of a constellation of abnormalities including neuropathological features that closely resemble those characterizing the neurodegeneration of Alzheimer disease. Because cultured cell lines from patients with Alzheimer disease and other neurodegenerations have a hypersensitivity to the lethal effects of DNA-damaging agents, we studied the response of Down syndrome lymphoblastoid lines to the lethal effects of ionizing and ultraviolet radiation. Lines from the four Down syndrome patients were more sensitive to X-rays than lines from 28 normal donors (P = 10(-4)), while survival of the Down syndrome lines after ultraviolet irradiation was not significantly different from normal. This hypersensitivity to X-rays, which may reflect defective repair of X-ray-induced DNA damage, represents the first abnormality common to cultured cells from both Down syndrome and Alzheimer disease patients.

Variables influencing growth and morphology of colonies of cells from human amniotic fluid.

Growth of cells from amniotic fluid was studied with respect to cell concentration in the inoculum, blood contamination of the fluid, fluid colour, fluid clarity, gestational age of the pregnancy, and growth factors. Dependent variables measured were colony formation, colony size, and colony morphology after 7, 11, and 14 days of culture. The following conclusions were established from these studies: small sample volumes are the most efficient for producing colonies; cells from very bloody or dark brown fluids have a slower rate of growth; growth of cells from cloudy (noncontaminated) fluids is better than growth of cells from clear fluids; the proportion of colonies that are epithelioid varies with gestational age; the stimulating effect of 100 ng/ml fibroblast growth factor on cells from amniotic fluid was confirmed.