Spot Scanning and Passive Scattering Proton Therapy: Relative Biological Effectiveness and Oxygen Enhancement Ratio in Cultured Cells
Purpose To determine the relative biological effectiveness (RBE), oxygen enhancement ratio (OER), and contribution of the indirect effect of spot scanning proton beams, passive scattering proton beams, or both in cultured cells in comparison with clinically used photons. Methods and Materials The RB...
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| creator | Iwata, Hiromitsu, MD, PhD Ogino, Hiroyuki, MD, PhD Hashimoto, Shingo, MD Yamada, Maho, MD Shibata, Hiroki, MS Yasui, Keisuke, MS Toshito, Toshiyuki, PhD Omachi, Chihiro, PhD Tatekawa, Kotoha, MD Manabe, Yoshihiko, MD, PhD Mizoe, Jun-etsu, MD, PhD Shibamoto, Yuta, MD, PhD |
| description | Purpose To determine the relative biological effectiveness (RBE), oxygen enhancement ratio (OER), and contribution of the indirect effect of spot scanning proton beams, passive scattering proton beams, or both in cultured cells in comparison with clinically used photons. Methods and Materials The RBE of passive scattering proton beams at the center of the spread-out Bragg peak (SOBP) was determined from dose-survival curves in 4 cell lines using 6-MV X rays as controls. Survival of 2 cell lines after spot scanning and passive scattering proton irradiation was then compared. Biological effects at the distal end region of the SOBP were also investigated. The OER of passive scattering proton beams and 6 MX X rays were investigated in 2 cell lines. The RBE and OER values were estimated at a 10% cell survival level. The maximum degree of protection of radiation effects by dimethyl sulfoxide was determined to estimate the contribution of the indirect effect against DNA damage. All experiments comparing protons and X rays were made under the same biological conditions. Results The RBE values of passive scattering proton beams in the 4 cell lines examined were 1.01 to 1.22 (average, 1.14) and were almost identical to those of spot scanning beams. Biological effects increased at the distal end of the SOBP. In the 2 cell lines examined, the OER was 2.74 (95% confidence interval, 2.56-2.80) and 3.08 (2.84-3.11), respectively, for X rays, and 2.39 (2.38-2.43) and 2.72 (2.69-2.75), respectively, for protons ( P |
| doi_str_mv | 10.1016/j.ijrobp.2016.01.017 |
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| fullrecord | <record><control><sourceid>proquest_osti_</sourceid><recordid>TN_cdi_osti_scitechconnect_22648619</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>1_s2_0_S0360301616000389</els_id><sourcerecordid>1781542547</sourcerecordid><originalsourceid>FETCH-LOGICAL-c511t-e1855bca728afa5c8971c6290321dbe1e56a6cad7a9173d0bb208310bf1874ad3</originalsourceid><addsrcrecordid>eNqFUk2LFDEQbURxx9V_IBLw4qXHVPrbg6DDrAoLu-ys4C2k09UzaXuSNkkvzg_Y_21irx68CAUhVa-qHu9VkrwEugYK5dthrQZr2mnNwm9NIUT1KFlBXTVpVhTfHicrmpU0zUL5LHnm3EApBajyp8kZq2idlxlbJfe7yXiyk0JrpfdE6I5cC-fUHcak92hj-toabzS5PaAV0-kducFR-Ij5qMxo9kqKkWz7HmVManTu96Crn6c9arLVB6ElHlF7chPaDFGabObRzxY7ssFxdM-TJ70YHb54eM-Trxfb283n9PLq05fNh8tUFgA-RaiLopWiYrXoRSHrpgJZsoZmDLoWAYtSlFJ0lWigyjratozWGdC2D6rkosvOk9fLXOO84k4qj_IgjdaBOWeszOsSmoB6s6Ama37M6Dw_KicDT6HRzI5DVUORsyKvAjRfoNIa5yz2fLLqKOyJA-XRJj7wxSYebeIUQsS2Vw8b5vaI3d-mP74EwPsFgEGNO4U2ksWgYqds5NoZ9b8N_w6Qo9LRqO94QjeY2eqgNAfuGKd8F08lXgqU4Uqyusl-AcW0u2k</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1781542547</pqid></control><display><type>article</type><title>Spot Scanning and Passive Scattering Proton Therapy: Relative Biological Effectiveness and Oxygen Enhancement Ratio in Cultured Cells</title><source>MEDLINE</source><source>Access via ScienceDirect (Elsevier)</source><creator>Iwata, Hiromitsu, MD, PhD ; Ogino, Hiroyuki, MD, PhD ; Hashimoto, Shingo, MD ; Yamada, Maho, MD ; Shibata, Hiroki, MS ; Yasui, Keisuke, MS ; Toshito, Toshiyuki, PhD ; Omachi, Chihiro, PhD ; Tatekawa, Kotoha, MD ; Manabe, Yoshihiko, MD, PhD ; Mizoe, Jun-etsu, MD, PhD ; Shibamoto, Yuta, MD, PhD</creator><creatorcontrib>Iwata, Hiromitsu, MD, PhD ; Ogino, Hiroyuki, MD, PhD ; Hashimoto, Shingo, MD ; Yamada, Maho, MD ; Shibata, Hiroki, MS ; Yasui, Keisuke, MS ; Toshito, Toshiyuki, PhD ; Omachi, Chihiro, PhD ; Tatekawa, Kotoha, MD ; Manabe, Yoshihiko, MD, PhD ; Mizoe, Jun-etsu, MD, PhD ; Shibamoto, Yuta, MD, PhD</creatorcontrib><description>Purpose To determine the relative biological effectiveness (RBE), oxygen enhancement ratio (OER), and contribution of the indirect effect of spot scanning proton beams, passive scattering proton beams, or both in cultured cells in comparison with clinically used photons. Methods and Materials The RBE of passive scattering proton beams at the center of the spread-out Bragg peak (SOBP) was determined from dose-survival curves in 4 cell lines using 6-MV X rays as controls. Survival of 2 cell lines after spot scanning and passive scattering proton irradiation was then compared. Biological effects at the distal end region of the SOBP were also investigated. The OER of passive scattering proton beams and 6 MX X rays were investigated in 2 cell lines. The RBE and OER values were estimated at a 10% cell survival level. The maximum degree of protection of radiation effects by dimethyl sulfoxide was determined to estimate the contribution of the indirect effect against DNA damage. All experiments comparing protons and X rays were made under the same biological conditions. Results The RBE values of passive scattering proton beams in the 4 cell lines examined were 1.01 to 1.22 (average, 1.14) and were almost identical to those of spot scanning beams. Biological effects increased at the distal end of the SOBP. In the 2 cell lines examined, the OER was 2.74 (95% confidence interval, 2.56-2.80) and 3.08 (2.84-3.11), respectively, for X rays, and 2.39 (2.38-2.43) and 2.72 (2.69-2.75), respectively, for protons ( P <.05 for both cells between X rays and protons). The maximum degree of protection was significantly higher for X rays than for proton beams ( P <.05). Conclusions The RBE values of spot scanning and passive scattering proton beams were almost identical. The OER was lower for protons than for X rays. The lower contribution of the indirect effect may partly account for the lower OER of protons.</description><identifier>ISSN: 0360-3016</identifier><identifier>EISSN: 1879-355X</identifier><identifier>DOI: 10.1016/j.ijrobp.2016.01.017</identifier><identifier>PMID: 27084632</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; BIOLOGICAL RADIATION EFFECTS ; BRAGG CURVE ; CELL CULTURES ; Cell Line ; Cell Survival - drug effects ; Cell Survival - radiation effects ; Colony-Forming Units Assay ; Cricetinae ; DNA Damage ; DNA DAMAGES ; Dose-Response Relationship, Radiation ; Hematology, Oncology and Palliative Medicine ; Humans ; Linear Energy Transfer ; Mice ; Oxygen - metabolism ; Oxygen - radiation effects ; OXYGEN ENHANCEMENT RATIO ; Photons ; PROTON BEAMS ; Proton Therapy ; Protons ; Radiation-Protective Agents - pharmacology ; Radiology ; RADIOLOGY AND NUCLEAR MEDICINE ; RADIOTHERAPY ; RBE ; Relative Biological Effectiveness ; Scattering, Radiation ; SOCIO-ECONOMIC FACTORS ; Sulfides - pharmacology ; SURVIVAL CURVES ; X RADIATION ; X-Rays</subject><ispartof>International journal of radiation oncology, biology, physics, 2016-05, Vol.95 (1), p.95-102</ispartof><rights>Elsevier Inc.</rights><rights>2016 Elsevier Inc.</rights><rights>Copyright © 2016 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c511t-e1855bca728afa5c8971c6290321dbe1e56a6cad7a9173d0bb208310bf1874ad3</citedby><cites>FETCH-LOGICAL-c511t-e1855bca728afa5c8971c6290321dbe1e56a6cad7a9173d0bb208310bf1874ad3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ijrobp.2016.01.017$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27084632$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/22648619$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Iwata, Hiromitsu, MD, PhD</creatorcontrib><creatorcontrib>Ogino, Hiroyuki, MD, PhD</creatorcontrib><creatorcontrib>Hashimoto, Shingo, MD</creatorcontrib><creatorcontrib>Yamada, Maho, MD</creatorcontrib><creatorcontrib>Shibata, Hiroki, MS</creatorcontrib><creatorcontrib>Yasui, Keisuke, MS</creatorcontrib><creatorcontrib>Toshito, Toshiyuki, PhD</creatorcontrib><creatorcontrib>Omachi, Chihiro, PhD</creatorcontrib><creatorcontrib>Tatekawa, Kotoha, MD</creatorcontrib><creatorcontrib>Manabe, Yoshihiko, MD, PhD</creatorcontrib><creatorcontrib>Mizoe, Jun-etsu, MD, PhD</creatorcontrib><creatorcontrib>Shibamoto, Yuta, MD, PhD</creatorcontrib><title>Spot Scanning and Passive Scattering Proton Therapy: Relative Biological Effectiveness and Oxygen Enhancement Ratio in Cultured Cells</title><title>International journal of radiation oncology, biology, physics</title><addtitle>Int J Radiat Oncol Biol Phys</addtitle><description>Purpose To determine the relative biological effectiveness (RBE), oxygen enhancement ratio (OER), and contribution of the indirect effect of spot scanning proton beams, passive scattering proton beams, or both in cultured cells in comparison with clinically used photons. Methods and Materials The RBE of passive scattering proton beams at the center of the spread-out Bragg peak (SOBP) was determined from dose-survival curves in 4 cell lines using 6-MV X rays as controls. Survival of 2 cell lines after spot scanning and passive scattering proton irradiation was then compared. Biological effects at the distal end region of the SOBP were also investigated. The OER of passive scattering proton beams and 6 MX X rays were investigated in 2 cell lines. The RBE and OER values were estimated at a 10% cell survival level. The maximum degree of protection of radiation effects by dimethyl sulfoxide was determined to estimate the contribution of the indirect effect against DNA damage. All experiments comparing protons and X rays were made under the same biological conditions. Results The RBE values of passive scattering proton beams in the 4 cell lines examined were 1.01 to 1.22 (average, 1.14) and were almost identical to those of spot scanning beams. Biological effects increased at the distal end of the SOBP. In the 2 cell lines examined, the OER was 2.74 (95% confidence interval, 2.56-2.80) and 3.08 (2.84-3.11), respectively, for X rays, and 2.39 (2.38-2.43) and 2.72 (2.69-2.75), respectively, for protons ( P <.05 for both cells between X rays and protons). The maximum degree of protection was significantly higher for X rays than for proton beams ( P <.05). Conclusions The RBE values of spot scanning and passive scattering proton beams were almost identical. The OER was lower for protons than for X rays. The lower contribution of the indirect effect may partly account for the lower OER of protons.</description><subject>Animals</subject><subject>BIOLOGICAL RADIATION EFFECTS</subject><subject>BRAGG CURVE</subject><subject>CELL CULTURES</subject><subject>Cell Line</subject><subject>Cell Survival - drug effects</subject><subject>Cell Survival - radiation effects</subject><subject>Colony-Forming Units Assay</subject><subject>Cricetinae</subject><subject>DNA Damage</subject><subject>DNA DAMAGES</subject><subject>Dose-Response Relationship, Radiation</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Humans</subject><subject>Linear Energy Transfer</subject><subject>Mice</subject><subject>Oxygen - metabolism</subject><subject>Oxygen - radiation effects</subject><subject>OXYGEN ENHANCEMENT RATIO</subject><subject>Photons</subject><subject>PROTON BEAMS</subject><subject>Proton Therapy</subject><subject>Protons</subject><subject>Radiation-Protective Agents - pharmacology</subject><subject>Radiology</subject><subject>RADIOLOGY AND NUCLEAR MEDICINE</subject><subject>RADIOTHERAPY</subject><subject>RBE</subject><subject>Relative Biological Effectiveness</subject><subject>Scattering, Radiation</subject><subject>SOCIO-ECONOMIC FACTORS</subject><subject>Sulfides - pharmacology</subject><subject>SURVIVAL CURVES</subject><subject>X RADIATION</subject><subject>X-Rays</subject><issn>0360-3016</issn><issn>1879-355X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUk2LFDEQbURxx9V_IBLw4qXHVPrbg6DDrAoLu-ys4C2k09UzaXuSNkkvzg_Y_21irx68CAUhVa-qHu9VkrwEugYK5dthrQZr2mnNwm9NIUT1KFlBXTVpVhTfHicrmpU0zUL5LHnm3EApBajyp8kZq2idlxlbJfe7yXiyk0JrpfdE6I5cC-fUHcak92hj-toabzS5PaAV0-kducFR-Ij5qMxo9kqKkWz7HmVManTu96Crn6c9arLVB6ElHlF7chPaDFGabObRzxY7ssFxdM-TJ70YHb54eM-Trxfb283n9PLq05fNh8tUFgA-RaiLopWiYrXoRSHrpgJZsoZmDLoWAYtSlFJ0lWigyjratozWGdC2D6rkosvOk9fLXOO84k4qj_IgjdaBOWeszOsSmoB6s6Ama37M6Dw_KicDT6HRzI5DVUORsyKvAjRfoNIa5yz2fLLqKOyJA-XRJj7wxSYebeIUQsS2Vw8b5vaI3d-mP74EwPsFgEGNO4U2ksWgYqds5NoZ9b8N_w6Qo9LRqO94QjeY2eqgNAfuGKd8F08lXgqU4Uqyusl-AcW0u2k</recordid><startdate>20160501</startdate><enddate>20160501</enddate><creator>Iwata, Hiromitsu, MD, PhD</creator><creator>Ogino, Hiroyuki, MD, PhD</creator><creator>Hashimoto, Shingo, MD</creator><creator>Yamada, Maho, MD</creator><creator>Shibata, Hiroki, MS</creator><creator>Yasui, Keisuke, MS</creator><creator>Toshito, Toshiyuki, PhD</creator><creator>Omachi, Chihiro, PhD</creator><creator>Tatekawa, Kotoha, MD</creator><creator>Manabe, Yoshihiko, MD, PhD</creator><creator>Mizoe, Jun-etsu, MD, PhD</creator><creator>Shibamoto, Yuta, MD, PhD</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>OTOTI</scope></search><sort><creationdate>20160501</creationdate><title>Spot Scanning and Passive Scattering Proton Therapy: Relative Biological Effectiveness and Oxygen Enhancement Ratio in Cultured Cells</title><author>Iwata, Hiromitsu, MD, PhD ; Ogino, Hiroyuki, MD, PhD ; Hashimoto, Shingo, MD ; Yamada, Maho, MD ; Shibata, Hiroki, MS ; Yasui, Keisuke, MS ; Toshito, Toshiyuki, PhD ; Omachi, Chihiro, PhD ; Tatekawa, Kotoha, MD ; Manabe, Yoshihiko, MD, PhD ; Mizoe, Jun-etsu, MD, PhD ; Shibamoto, Yuta, MD, PhD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c511t-e1855bca728afa5c8971c6290321dbe1e56a6cad7a9173d0bb208310bf1874ad3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>BIOLOGICAL RADIATION EFFECTS</topic><topic>BRAGG CURVE</topic><topic>CELL CULTURES</topic><topic>Cell Line</topic><topic>Cell Survival - drug effects</topic><topic>Cell Survival - radiation effects</topic><topic>Colony-Forming Units Assay</topic><topic>Cricetinae</topic><topic>DNA Damage</topic><topic>DNA DAMAGES</topic><topic>Dose-Response Relationship, Radiation</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Humans</topic><topic>Linear Energy Transfer</topic><topic>Mice</topic><topic>Oxygen - metabolism</topic><topic>Oxygen - radiation effects</topic><topic>OXYGEN ENHANCEMENT RATIO</topic><topic>Photons</topic><topic>PROTON BEAMS</topic><topic>Proton Therapy</topic><topic>Protons</topic><topic>Radiation-Protective Agents - pharmacology</topic><topic>Radiology</topic><topic>RADIOLOGY AND NUCLEAR MEDICINE</topic><topic>RADIOTHERAPY</topic><topic>RBE</topic><topic>Relative Biological Effectiveness</topic><topic>Scattering, Radiation</topic><topic>SOCIO-ECONOMIC FACTORS</topic><topic>Sulfides - pharmacology</topic><topic>SURVIVAL CURVES</topic><topic>X RADIATION</topic><topic>X-Rays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Iwata, Hiromitsu, MD, PhD</creatorcontrib><creatorcontrib>Ogino, Hiroyuki, MD, PhD</creatorcontrib><creatorcontrib>Hashimoto, Shingo, MD</creatorcontrib><creatorcontrib>Yamada, Maho, MD</creatorcontrib><creatorcontrib>Shibata, Hiroki, MS</creatorcontrib><creatorcontrib>Yasui, Keisuke, MS</creatorcontrib><creatorcontrib>Toshito, Toshiyuki, PhD</creatorcontrib><creatorcontrib>Omachi, Chihiro, PhD</creatorcontrib><creatorcontrib>Tatekawa, Kotoha, MD</creatorcontrib><creatorcontrib>Manabe, Yoshihiko, MD, PhD</creatorcontrib><creatorcontrib>Mizoe, Jun-etsu, MD, PhD</creatorcontrib><creatorcontrib>Shibamoto, Yuta, MD, PhD</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>OSTI.GOV</collection><jtitle>International journal of radiation oncology, biology, physics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Iwata, Hiromitsu, MD, PhD</au><au>Ogino, Hiroyuki, MD, PhD</au><au>Hashimoto, Shingo, MD</au><au>Yamada, Maho, MD</au><au>Shibata, Hiroki, MS</au><au>Yasui, Keisuke, MS</au><au>Toshito, Toshiyuki, PhD</au><au>Omachi, Chihiro, PhD</au><au>Tatekawa, Kotoha, MD</au><au>Manabe, Yoshihiko, MD, PhD</au><au>Mizoe, Jun-etsu, MD, PhD</au><au>Shibamoto, Yuta, MD, PhD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Spot Scanning and Passive Scattering Proton Therapy: Relative Biological Effectiveness and Oxygen Enhancement Ratio in Cultured Cells</atitle><jtitle>International journal of radiation oncology, biology, physics</jtitle><addtitle>Int J Radiat Oncol Biol Phys</addtitle><date>2016-05-01</date><risdate>2016</risdate><volume>95</volume><issue>1</issue><spage>95</spage><epage>102</epage><pages>95-102</pages><issn>0360-3016</issn><eissn>1879-355X</eissn><abstract>Purpose To determine the relative biological effectiveness (RBE), oxygen enhancement ratio (OER), and contribution of the indirect effect of spot scanning proton beams, passive scattering proton beams, or both in cultured cells in comparison with clinically used photons. Methods and Materials The RBE of passive scattering proton beams at the center of the spread-out Bragg peak (SOBP) was determined from dose-survival curves in 4 cell lines using 6-MV X rays as controls. Survival of 2 cell lines after spot scanning and passive scattering proton irradiation was then compared. Biological effects at the distal end region of the SOBP were also investigated. The OER of passive scattering proton beams and 6 MX X rays were investigated in 2 cell lines. The RBE and OER values were estimated at a 10% cell survival level. The maximum degree of protection of radiation effects by dimethyl sulfoxide was determined to estimate the contribution of the indirect effect against DNA damage. All experiments comparing protons and X rays were made under the same biological conditions. Results The RBE values of passive scattering proton beams in the 4 cell lines examined were 1.01 to 1.22 (average, 1.14) and were almost identical to those of spot scanning beams. Biological effects increased at the distal end of the SOBP. In the 2 cell lines examined, the OER was 2.74 (95% confidence interval, 2.56-2.80) and 3.08 (2.84-3.11), respectively, for X rays, and 2.39 (2.38-2.43) and 2.72 (2.69-2.75), respectively, for protons ( P <.05 for both cells between X rays and protons). The maximum degree of protection was significantly higher for X rays than for proton beams ( P <.05). Conclusions The RBE values of spot scanning and passive scattering proton beams were almost identical. The OER was lower for protons than for X rays. The lower contribution of the indirect effect may partly account for the lower OER of protons.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>27084632</pmid><doi>10.1016/j.ijrobp.2016.01.017</doi><tpages>8</tpages></addata></record> |
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| subjects | Animals BIOLOGICAL RADIATION EFFECTS BRAGG CURVE CELL CULTURES Cell Line Cell Survival - drug effects Cell Survival - radiation effects Colony-Forming Units Assay Cricetinae DNA Damage DNA DAMAGES Dose-Response Relationship, Radiation Hematology, Oncology and Palliative Medicine Humans Linear Energy Transfer Mice Oxygen - metabolism Oxygen - radiation effects OXYGEN ENHANCEMENT RATIO Photons PROTON BEAMS Proton Therapy Protons Radiation-Protective Agents - pharmacology Radiology RADIOLOGY AND NUCLEAR MEDICINE RADIOTHERAPY RBE Relative Biological Effectiveness Scattering, Radiation SOCIO-ECONOMIC FACTORS Sulfides - pharmacology SURVIVAL CURVES X RADIATION X-Rays |
| title | Spot Scanning and Passive Scattering Proton Therapy: Relative Biological Effectiveness and Oxygen Enhancement Ratio in Cultured Cells |
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