Effect of low dose rate irradiation on the division potential of cells in vitro. VI. Changes in DNA and in radiosensitivity during aging of human fobroblasts.

The sensitivity to low dose rate ionizing radiation increases progressively through the lifespan of human embryonic lung fibroblasts. There is also an increase in the number of alkali-sensitive sites leading to an increase in single-strand breaks and in DNA with low molecular weight during cell lysis. These DNA changes become pronounced at the very end of the lifespan. The correlation between aging, increased radiosensitivity and accumulation of DNA damage is discussed.

Effect of low-dose-rate irradiation on the division potential of cells in vitro. V. Human skin fibroblasts from donors with a high risk of cancer.

Skin fibroblasts from normal donors, donors with ataxia-telangiectasia or Fanconi's anemia, and from 1 cancer patient were treated with repeated gamma-radiation at about 16 rads per hour. The remaining division potential of all fibroblasts, except for the Fanconi's anemia cells, was reduced to different extents by radiation. The growth potential of Fanconi's anemia cells was increased in all the irradiated cultures. The increase was 54% in the group that survived the longest. These results were identical to those obtained with fibroblasts from certain species that have a high probability of transformation.

Inhibition of pyrimidine incorporation without inhibition of DNA synthesis.

A putative lymphocytic chalone was tested measuring the incorporation of purine and pyrimidine nucleosides and by cytophotometry. The pyrimidine precursors were inhibited but not the purines. Thymidine and deoxycytidine incorporation even performed simultaneously with cytophotometry can be misleading in the analysis of the inhibition of cell division.

Effects of low dose rate irradiation on the division potential of cells in vitro. IV. Embryonic and adult human lung fibroblast-like cells.

Early and late passage human embryonic lung fibroblasts were compared with early passage adult lung fibroblasts with regards to their survival (number of population doublings), after low dose rate ionizing radiation. It was found that early passage embryonic cells are quite resistant to this type of radiation. Late passage embryonic and early passage adult fibroblasts are more sensitive to ionizing radiations. The results suggest that cell aging is accompanied by an increased sensitivity to low dose rate ionizing radiation and favor the idea that aging in vitro, expressed as a function of the fibroblast division potential, is correlated with aging in vivo.

Lack of DNA synthesis inhibitory activity in an immunosuppressor obtained from spleen.

A tissue extract derived from bovine spleen which is an immunosuppressor in vivo inhibits the incorporation of the two DNA pyrimidine nucleosides but does not inhibit the incorporation of purine nucleosides. The results indicate that the immunosuppressive action of the spleen extract is not mediated via inhibition of cell division.

Concept of fibroblast aging in vitro: implications for cell biology.

Aging in vitro is defined as the progressive growth decline of mass populations of fibroblastlike cells leading to their eventual loss after serial subcultivations. Different species are compared in terms of the doubling potential of their fibroblasts in culture. A gradient like behavior is found with at one end species whose fibroblasts invariably die after a certain number of doublings and at the other end species yielding fibroblasts with infinite growth potential. The relationship of this phenomenon with cancer and aging is reviewed and discussed. The response of chicken, mouse and human fibroblasts to slow dose rate ionizing radiation fits with the relative positions of these species on the scale relating the probability of yielding fibroblastic populations with infinite life spans. This difference between fibroblastlike cultures is interpreted in terms of the presence or absence of repair mechanisms or of a repairable substrate. The growth potential of fibroblasts in vitro seems to be related to their susceptibility to viral, chemical and physical oncogenes, and could have important implications for the study of evolution.