An ex vivo organ culture screening model revealed that low temperature conditions prevent side effects of anticancer drugs

• Published in: Scientific reports Vol. 12; no. 1; p. 3093
• Main Authors: Tian, Tian, Miyazaki, Kanako, Chiba, Yuta, Funada, Keita, Yuta, Tomomi, Mizuta, Kanji, Fu, Yao, Kawahara, Jumpei, Han, Xue, Ando, Yuna, Funada, Ami, Yamada, Aya, Iwamoto, Tsutomu, Nakamura, Seiji, Takahashi, Ichiro, Fukumoto, Satoshi, Yoshizaki, Keigo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23.02.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/136/2060; 692/308/1426; Antineoplastic Agents - adverse effects; Antineoplastic drugs; Antitumor agents; Apoptosis; Cancer; Cell culture; Cell cycle; Cell Cycle Checkpoints - drug effects; Cell Proliferation - drug effects; Chemotherapy; Cyclophosphamide; Cyclophosphamide - adverse effects; Deoxyribonucleic acid; DNA; DNA biosynthesis; DNA damage; DNA Damage - drug effects; DNA Replication - drug effects; Drug development; Drugs; G1 phase; G1 Phase - drug effects; Humanities and Social Sciences; Humans; Hypoplasia; Low temperature; Models, Biological; multidisciplinary; Organ culture; Organ Culture Techniques; Phosphorylation; Science; Science (multidisciplinary); Side effects; Temperature
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-06945-7

Development of chemotherapy has led to a high survival rate of cancer patients; however, the severe side effects of anticancer drugs, including organ hypoplasia, persist. To assume the side effect of anticancer drugs, we established a new ex vivo screening model and described a method for suppressing side effects. Cyclophosphamide (CPA) is a commonly used anticancer drug and causes severe side effects in developing organs with intensive proliferation, including the teeth and hair. Using the organ culture model, we found that treatment with CPA disturbed the growth of tooth germs by inducing DNA damage, apoptosis and suppressing cellular proliferation and differentiation. Furthermore, low temperature suppressed CPA-mediated inhibition of organ development. Our ex vivo and in vitro analysis revealed that low temperature impeded Rb phosphorylation and caused cell cycle arrest at the G1 phase during CPA treatment. This can prevent the CPA-mediated cell damage of DNA replication caused by the cross-linking reaction of CPA. Our findings suggest that the side effects of anticancer drugs on organ development can be avoided by maintaining the internal environment under low temperature.