Differing Levels of Excision Repair in Human Fetal Dermis and Brain Cells

Abstract

Abstract— The levels of DNA excision repair, as measured by unscheduled DNA synthesis (UDS) and the UV‐endonuclease sensitive site assay, were compared in cells derived from human fetal brain and dermal tissues. The level of UDS induced following ultraviolet (UV) irradiation was found to be lower (approx. 60%) in the fetal brain cells than in fetal dermal cells. It was determined, using the UV‐endonuclease sensitive site assay to confirm the UDS observation, that 50% of the dimers induced by UV in fetal dermal cells were repaired in 8h, while only 15% were removed in the fetal brain cells during the same period of time. Even after 24 h, only 44% of the dimers induced by UV in the fetal brain cells were repaired, while 65% were removed in the dermal cells. These data suggest that cultured human fetal brain cells exhibit lower levels of excision repair compared to cultured human fetal dermal cells.

Quantitation of Pyrimidine Dimers by Immunoslot Blot Following Sublethal Uv‐irradiation of Human Cells

“…Human cells are highly proficient for the excision repair of pyrimidine dimers following U V irradiation. Most in vitro studies utilizing normal human skin fibroblasts in culture indicate 50% removal of pyrimidine dimers in 6 to 12 h (Gibson and D'Ambrosio, 1982;Gibson-D'Ambrosio et al, 1983;Konze-Thomas et al, 1979;Ahmed et al, 1977;Bohr et al, 1986) following exposures between 5 and 25 J m-2 U V radiation. Our studies using the ISB assay for dimer induction by 2 and 5 J m-2 U V radiation are consistent i.e.…”

“…The number of dimers induced per J m-> UV radiation was determined using the M . lurelcs UV-endonuclease and human skin fibroblasts irradiated with 10 J m-* UV radiation as described earlier (Gibson-D'Ambrosio et al, 1983;Gibson and D'Ambrosio, 1982).…”

“…Several methodologies have been used for the detection of pyrimidine dimers in irradiated cellular DNA (Freidberg andHanawalt, 1981, 1983). It has been established that normal human cells in vitro and in vivo exhibit a high level of excision repair of UV radiation induced pyrimidine dimers (Gibson and D'Ambrosio, 1982;Gibson-D'Ambrosio et al, 1983;Konze-Thomas et al, 1979;Ahmed et al, 1977;Bohr et al, 1986;Sutherland et al, 1980b;D'Amrosio et al, 1981a). Most of these studies require large number of cells, radiolabelled DNA and/or lethal doses of UV radiation.…”

Critical windows of exposure for children's health: cancer in human epidemiological studies and neoplasms in experimental animal models.

“…Repair of 06-methylguanine was lower and levels of this adduct higher in newborn mice compared to adults given the same dose of N-nitrosodimethylamine (NDMA) (174). Human fetal cells in early passage showed differences in the extent of DNA excision repair after ultraviolet irradiation or ENU; skin and intestine were more active than liver, kidney, and brain (175). However, certain other DNA repair enzymes are quite active in fetal tissues.…”

Benzamide prevention of ultraviolet radiation‐induced transformation as measured by anchorage‐independent growth and the absence of correlation with thymidine dimer formation and DNA repair

“…HNSF were incubated with either 2 pCi/ml [3H3C]thymidine (specific activity 6.7 mCi/mmole) or [I4C]thymidine (specific activity 450 pCi/mmole) for 48 hr as described previously [28,29]. The labeled cells were removed from the surface of the plates with trypsin and seeded onto 25 cm' Corning tissue culture dishes at a density of 3 X lo3 cells/cm*.…”