Harding-Passey melanoma cells in monolayer culture (HPM-73 line) were treated during exponential growth phase with single doses of X-rays (85 kV) from 2 up to 16 Gy (200 to 1600 rd). While 2 or 4 Gy resulted in a growth retardation (up to 2 days) followed by resumption of proliferation thereafter, 8 Gy, and still more pronounced 16 Gy, resulted in a significant decrease of the survival rate (till about 5 to 10% after 8 Gy). In the course of several days after 8 or 16 Gy numerous large cells--in comparison with controls--were formed, and following exposure to 8 Gy the average cellular protein content had more than doubled (and after 16 Gy more than tripled) in the course of 11 days. The inhibitory effect of X-irradiation on cell multiplication was significantly augmented by continuous incubation in culture media containing either quinacrine (atebrine) or chloroquine (resochine) in concentrations (3-6 X 10(-6)M) which in itself were not or only little inhibitory. Especially noteworthy was the death of all cells in cultures irradiated with 8 Gy and incubated for several weeks with 6 X 10(-6)M quinacrine or chloroquine. Also, treatment with 6 X 10(-6)M chloroquine of cultures irradiated with 4 Gy resulted in death of all cells. The specific melanin content (E400/10(6) cells or E400/mg cell protein) of cultures significantly increased several days after X-ray irradiation. Also, treatment with chloroquine (but not with quinacrine) resulted in an increased melanin content which was most strikingly increased after the combined treatment of irradiation and chloroquine. The effects of quinacrine and chloroquine on pre-irradiated cells were discussed under the aspect of the well-known inhibitory action of these substances on DNA-synthesis, especially in connection with DNA repair processes.

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