Phosphatidylserine induces apoptosis in CHO cells without mitochondrial dysfunction in a manner dependent on caspases other than caspases-1, -3, -8 and -9.

Treatment of Chinese hamster ovary K1 cells with phosphatidylserine (PS) caused typical　apoptosis with distinct morphological and biochemical features in a dose- and time-dependent manner. However, unlike camptothecin-induced apoptosis, changes in mitochondrial transmembranepotential were not observed. In addition, cytochrome c release did not occur in PS-induced apoptosis. A pan caspase inhibitor, Z-VAD, significantly inhibited the apoptosis, but inhibitors of caspase-1, -3, -8 and -9 did not. Activities of caspase-1, -3, -8 and -9 were increased bytreatment of the cells with camptothecin, but not with PS. These results suggest that PS-induced apoptosis occurs without the collapse of mitochondrial transmembrane potential and without the release of cytochrome c, in a manner independent of caspase-1, -3, -8 and -9

Radioresistance of mouse intestine induced by carbon-ion irradiation

The purpose of this paper is to report that gut crypt cells become radioresistant after single or fractionated irradiation with intermediate LET carbon ions. C3H female mice received whole body irradiation with 20 keV/mm carbon ions, and served the jejunum for crypt survival assay 3.5 days after irradiation. Dose-crypt survival relationship showed that the D0 value increased from 1.06 Gy to 1.94 Gy when the first dose of 9.0 Gy was followed by single graded doses of carbon ions with an interval time of 4 hr. The Increased D0 gradually decreased with a half decay time of 50 hr, and returned to 1.08 Gy, a similar value of single irradiation. When mice received 1 Gy carbon ions for 9 fractions with an interval time of 4 hr each, the D0 value of crypt cells surviving the preceding total dose of 9 Gy also increased to 1.89 Gy. The D0 increase was less prominent when the size of first or preceding dose was small. It is concluded that charged particles with intermediate LET produce a unique biological response, and would be beneficial for radiotherapy of visceral tumors.ICR

Biological gain of carbon-ion radiotherapy for the early response of tumor growth delay and agains aerly response of skin reaction in mice

The biological effectiveness of carbon ions relative to γ rays (RBE) was compared between the tumor growth delay and an early skin reaction of syngeneic mice. The RBE was larger for a tumor than skin when irradiated with large doses of high-LET (linear energy transfer) carbon ions. The intra-track damage (a term of a linear quadratic model) of a tumor and skin increased equally with an increase of the LET, while the inter-track damage (β term) of skin alone increased with the LET. These data provide evidence that high-LET radiotherapy could achieve therapeutic gain by minimizing the difference in response to fractionated irradiation between the tumor and normal tissue