Radiation-induced thymine base damage and its excision repair in active and inactive chromatin of HeLa cells.

The extent of production and excision repair of 5,6-dihydroxydihydrothymine type base (t') damage was determined in transcriptionally active and inactive chromatin of HeLa cells after exposure to 6.8 MeV electrons. It was observed that not only the yield but also rate of repair of t' products was greater in the active chromatin compared to the inactive chromatin of HeLa cells. The results strongly indicate that the conformation of chromatin is an important factor in determining the sensitivity to radiation damage and accessibility to enzymes required for repair of such damage.

Age associated alteration in DNA damage and repair capacity in Turbatrix aceti exposed to ionizing radiation.

Excision repair capacity was measured in young and old Turbatrix aceti (phylum Nematoda) following exposure to ionizing radiation. Both repair synthesis and removal of 5,6-dihydroxydihydrothymine type (glycol) base damage were quantitated. At least two-fold higher glycol levels were produced in the DNA of young than of old nematodes for the same radiation dose. Young worms also excised glycol damage more rapidly and completely than old worms. Both peak repair synthesis activity and completion of repair synthesis occurred at earlier times during post-irradiation incubation in young nematodes. The data indicate there is a significant age-associated difference in both the incidence and removal of ionizing radiation damage in T. aceti which is used as a model of the ageing process.

Age-related changes in the excision repair capacity of Turbatrix aceti.

Excision repair capacity was measured in the free-living nematode Turbatrix aceti, a model aging system. Excision repair was assessed by both repair synthesis activity and the actual removal of pyrimidine dimers from the genome. The young organisms removed lesions more rapidly and completely than the old for all fluences tested. Repair synthesis began and peaked earlier for young nematodes than old. The data consistently indicated a decline in DNA excision repair capacity with age in the nematode.

Production and excision repair of cyclobutane-type pyrimidine dimers in the DNA of Turbatrix aceti.

The production and removal of 254 nm ultraviolet-induced pyrimidine dimers was measured in the DNA of the free-living nematode Turbatrix aceti. Approximately 0.0035 per cent pyrimidine dimers are produced per J/m2. Following a fluence of 100 Jm2, approximately 50 per cent of the dimeric photoproducts were excised within 60 min. The number of pyrimidine dimers excised did not change with increasing U.V. fluence, indicating saturation of the U.V. repair system in T. aceti. The results indicate a highly efficient and selective repair system in Turbatrix aceti for dimeric photoproducts.

Relationship between cytotoxicity and DNA damage in mammalian cells treated with anthracenedione derivatives.

The effects of two anthracenedione derivatives on in vitro cell survival and DNA of Chinese hamster ovary (CHO) cells were investigated. The two drugs studied were 1,4-dihydroxy-5,8-bis-(2-[2-hydroxyethyl)amino)ethylamino)-9,10-anthracenedione (DHAQ, NSC No. 279836) and 1,4-bis-(2-[2-hydroxyethyl)-amino)ethylamino)-9,10-anthracenedione (HAQ, NSC No. 287513). DHAQ was 100-fold more potent in reducing cell survival than HAQ. DNA strand breaks were assayed by alkaline elution. DHAQ (10 ng/ml) caused more strand breakage than 1000 ng/ml HAQ. This difference correlates well with their differences in ability to kill cells.

Effect of cordycepin(3'-deoxyadenosine) on excision repair of 5,6-dihydroxy-dihydrothymine-type products from the DNA of Micrococcus radiodurans.

Cordycepin(3'-deoxyadenosine), a nucleoside analog, has been shown to enhance radiation-induced cell killing. In an effort to elucidate the possible mechanism for enhancement of cell killing, the effect of cordycepin on the excision repair of radiation-induced 5,6-dihydroxy-dihydrothymine-type (t') products from the DNA of wild type Micrococcus radiodurans was investigated. The capacity of M. radiodurans to excise nondimeric (t') products from its DNA was significantly impaired after cordycepin treatment. The results suggest that the increased radiation sensitivity of cordycepin-treated cells could be due to alterations in cellular processes that repair DNA damage.