Time‐lapse video reveals immediate heterogeneity and heritable damage among human ileocecal carcinoma HCT‐8 cells treated with raltitrexed (ZD1694)

Harry K. Slocum; John C. Parsons; Elva O. Winslow; Lori Broderick; Hans Minderman; Károly Tóth; William R. Greco; Youcef M. Rustum

doi:10.1002/1097-0320(20001201)41:4<252::AID-CYTO3>3.0.CO;2-X

Journal article

Time‐lapse video reveals immediate heterogeneity and heritable damage among human ileocecal carcinoma HCT‐8 cells treated with raltitrexed (ZD1694)

Harry K. Slocum, John C. Parsons, Elva O. Winslow, Lori Broderick, Hans Minderman, Károly Tóth, William R. Greco and Youcef M. Rustum

Cytometry (New York, N.Y.), Vol.41(4), pp.252-260

12/01/2000

DOI: 10.1002/1097-0320(20001201)41:4<252::AID-CYTO3>3.0.CO;2-X

PMID: 11084610

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Abstract

Background Cellular heterogeneity in drug response has important clinical implications, and is believed to develop over many generations during clonal evolution in human tumors. The purpose of this study was to determine the level of heterogeneity exhibited by sister cells soon after their birth. Methods Human ileocecal carcinoma cells (HCT‐8) were followed up to 11 days in vitro after a 2‐h exposure to 1 μM raltitrexed (IC95) in a time‐lapse video system. Results Over five experiments, 414 cells were followed after exposure to raltitrexed. Immediate sterility occurred in 74% of treated cells. Only 6% of cells could produce more than two generations of offspring, and heterogeneity in drug response was seen. Comparing sister cells < 24 h old, the more proliferative sibling produced up to 73 times more offspring, with a median ratio of 9.0 (control median = 1.19). Offspring of prolific drug‐treated cells had a decreased probability of division (68% compared with 92%) and an increased average interdivision time (19.0 h compared with 15.1 h). Conclusions Short‐term exposure to raltitrexed resulted in increased interdivision times and production of sterile offspring extending seven generations. Cellular heterogeneity (difference in proliferation potential comparing drug‐treated sister cells) was evident without a period of clonal evolution. Cytometry 41:252–260, 2000. © 2000 Wiley‐Liss, Inc.

cell culture

colorectal carcinoma

heterogeneity

inheritable damage

raltitrexed

thymidylate synthase inhibitor

time‐lapse video

Details

Title: Subtitle: Time‐lapse video reveals immediate heterogeneity and heritable damage among human ileocecal carcinoma HCT‐8 cells treated with raltitrexed (ZD1694)
Creators: Harry K. Slocum - Roswell Park Cancer Institute
John C. Parsons - Roswell Park Cancer Institute
Elva O. Winslow - Roswell Park Cancer Institute
Lori Broderick - Roswell Park Cancer Institute
Hans Minderman - Roswell Park Cancer Institute
Károly Tóth - Roswell Park Cancer Institute
William R. Greco - Roswell Park Cancer Institute
Youcef M. Rustum - Roswell Park Cancer Institute
Resource Type: Journal article
Publication Details: Cytometry (New York, N.Y.), Vol.41(4), pp.252-260
DOI: 10.1002/1097-0320(20001201)41:4<252::AID-CYTO3>3.0.CO;2-X
PMID: 11084610
NLM abbreviation: Cytometry
ISSN: 0196-4763
eISSN: 1097-0320
Publisher: John Wiley & Sons, Inc
Number of pages: 9
Grant note: NIH (CA16056; CA65761; RR10742) Roswell Park Alliance Foundation
Language: English
Date published: 12/01/2000
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984359898202771

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