Molecular radiobiology of human cell lines

Journal Article · Tue May 01 04:00:00 EDT 1962 · Journal of Molecular Biology

DOI:https://doi.org/10.1016/S0022-2836(62)80014-X· OSTI ID:4791647

Ragni, G.; Szybalski, Waclaw

A comparison was made of the intrinsic sensitivities to P³² decay of bacteriophage and bacterial deoxyribonucleic acid (DNA) with that of the more complex, diploid (or hyperdiploid) mammalian cells. The experiments throw new light on the nature of the P³²-DNA inactivation process and also confirm earlier notions on the mechanism of the radiosensitization of DNA halogenation. Compared with bacteria or phages, human cells were found to be highly resistant to this type of inactivation, with cell death ensuing after 4000 P³² to S³² transmutation events within the DNA complement of the cell (efficiency of killing, alpha = 2.4 x 10^-4). Incorporation of thymidine analogs, 5- chloro -, 5-bromo-, and 5-iododeoxyuridine (CUdR, BUdR, and IUdR), into the cell DNA increases the sensitivity to P/sup 32/decay inactivation by a factor of 2.1 (CUdR and BUdR) to 3.3 (IUdR) under the experimental conditions employed (60% thymidine replaced by the analogs). Studies on the mechanism of the phenomenon revealed that enhancement of the cell's sensitivity to the lethal effects of P³² decay requires that the halogen atoms be incorporated into the strand opposite to that bearing the P³² atoms. In other words, unifilar halogen labeling of the same DNA strand as that bearing the P³² atoms, while the other strand remains unlabeled (achieved by placing the cells in P³²- and BUdR-containing medium for only one round of DNA replication), does not alter the rate of cells inactivation observed with unifilar P³² labeling alone. These data indicate that scissions through both strands of the DNA molecule constitute the lethal events, and that the halogen, by its electrostatic interaction with the proximate P atom labilizes the phosphate-ester bond, and thus enhances the probability of the double chain scission event. The low killing efficiency of DNA-incorporated P³² for mammalian cells indicates either that the double scission occurs oniy rarely in the vulnerable regions of the DNA complement, i.e., those regions indispensable for cell growth under tissue culture conditions or that some very effective mechanism exists for repair of a constant fraction of the molecular lesions or for annulment of their lethal consequences by other means.

• Research Organization: Univ. of Wisconsin, Madison
• Sponsoring Organization: USDOE
• NSA Number: NSA-16-028786
• OSTI ID: 4791647
• Journal Information: Journal of Molecular Biology, Journal Name: Journal of Molecular Biology Journal Issue: 5 Vol. 4; ISSN 0022-2836
• Publisher: Elsevier
• Country of Publication: Country unknown/Code not available
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMAL CELLS
BACTERIA
BACTERIOPHAGES
BETA DECAY
BIOCHEMISTRY
CHROMOSOMES
HALOGENS
MAN
NUCLEIC ACIDS
PHOSPHORUS 32
QUANTITY RATIO
RADIOBIOLOGY
RADIOSENSITIVITY
SULFUR 32