Changes in drug sensitivity of a human astrocytoma clone previously treated with 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea in vitro

Sam C. Barranco, Courtney Townsend, Vernon K. Jenkins, Steven K. Koester, Barbara Y. Ho, Karen J. Reumont

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

We have shown in earlier studies that repeated weekly exposures of a human astrocytoma clone (AST 3-4) to MeCCNU (10 μg/ml for 1 h per week) produced a linear decrease in survival over the first 3 weekly treatments. But, after that time these cells became progressively more resistant to the 10 μg/ml concentration of the agent. In the studies reported here we show that these previously treated cells were also less responsive to other doses ranging from 1 to 30 μg MeCCNU/ml. This change in sensitivity to MeCCNU was accompanied by collateral changes in response to other agents: resistance to BCNU and Galactitol, increased sensitivity to Adriamycin, and no change to ionizing radiation. These experiments suggest that once repeated treatments with a single agent cause a tumor cell population to become more resistant, sensitivity to other agents may also change unpredictably.

Original languageEnglish (US)
Pages (from-to)293-298
Number of pages6
JournalInvestigational New Drugs
Volume6
Issue number4
DOIs
StatePublished - Dec 1988

Fingerprint

Semustine
Astrocytoma
Clone Cells
Galactitol
Pharmaceutical Preparations
Carmustine
Ionizing Radiation
Doxorubicin
Survival
Population
In Vitro Techniques
Neoplasms

Keywords

  • adriamycin
  • astrocytoma
  • drug resistance
  • nitrosourea
  • radiation

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

Cite this

Changes in drug sensitivity of a human astrocytoma clone previously treated with 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea in vitro. / Barranco, Sam C.; Townsend, Courtney; Jenkins, Vernon K.; Koester, Steven K.; Ho, Barbara Y.; Reumont, Karen J.

In: Investigational New Drugs, Vol. 6, No. 4, 12.1988, p. 293-298.

Research output: Contribution to journalArticle

Barranco, Sam C. ; Townsend, Courtney ; Jenkins, Vernon K. ; Koester, Steven K. ; Ho, Barbara Y. ; Reumont, Karen J. / Changes in drug sensitivity of a human astrocytoma clone previously treated with 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea in vitro. In: Investigational New Drugs. 1988 ; Vol. 6, No. 4. pp. 293-298.
@article{5fe41ad6aca5426fac03a69240031df5,
title = "Changes in drug sensitivity of a human astrocytoma clone previously treated with 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea in vitro",
abstract = "We have shown in earlier studies that repeated weekly exposures of a human astrocytoma clone (AST 3-4) to MeCCNU (10 μg/ml for 1 h per week) produced a linear decrease in survival over the first 3 weekly treatments. But, after that time these cells became progressively more resistant to the 10 μg/ml concentration of the agent. In the studies reported here we show that these previously treated cells were also less responsive to other doses ranging from 1 to 30 μg MeCCNU/ml. This change in sensitivity to MeCCNU was accompanied by collateral changes in response to other agents: resistance to BCNU and Galactitol, increased sensitivity to Adriamycin, and no change to ionizing radiation. These experiments suggest that once repeated treatments with a single agent cause a tumor cell population to become more resistant, sensitivity to other agents may also change unpredictably.",
keywords = "adriamycin, astrocytoma, drug resistance, nitrosourea, radiation",
author = "Barranco, {Sam C.} and Courtney Townsend and Jenkins, {Vernon K.} and Koester, {Steven K.} and Ho, {Barbara Y.} and Reumont, {Karen J.}",
year = "1988",
month = "12",
doi = "10.1007/BF00173647",
language = "English (US)",
volume = "6",
pages = "293--298",
journal = "Investigational New Drugs",
issn = "0167-6997",
publisher = "Kluwer Academic Publishers",
number = "4",

}

TY - JOUR

T1 - Changes in drug sensitivity of a human astrocytoma clone previously treated with 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea in vitro

AU - Barranco, Sam C.

AU - Townsend, Courtney

AU - Jenkins, Vernon K.

AU - Koester, Steven K.

AU - Ho, Barbara Y.

AU - Reumont, Karen J.

PY - 1988/12

Y1 - 1988/12

N2 - We have shown in earlier studies that repeated weekly exposures of a human astrocytoma clone (AST 3-4) to MeCCNU (10 μg/ml for 1 h per week) produced a linear decrease in survival over the first 3 weekly treatments. But, after that time these cells became progressively more resistant to the 10 μg/ml concentration of the agent. In the studies reported here we show that these previously treated cells were also less responsive to other doses ranging from 1 to 30 μg MeCCNU/ml. This change in sensitivity to MeCCNU was accompanied by collateral changes in response to other agents: resistance to BCNU and Galactitol, increased sensitivity to Adriamycin, and no change to ionizing radiation. These experiments suggest that once repeated treatments with a single agent cause a tumor cell population to become more resistant, sensitivity to other agents may also change unpredictably.

AB - We have shown in earlier studies that repeated weekly exposures of a human astrocytoma clone (AST 3-4) to MeCCNU (10 μg/ml for 1 h per week) produced a linear decrease in survival over the first 3 weekly treatments. But, after that time these cells became progressively more resistant to the 10 μg/ml concentration of the agent. In the studies reported here we show that these previously treated cells were also less responsive to other doses ranging from 1 to 30 μg MeCCNU/ml. This change in sensitivity to MeCCNU was accompanied by collateral changes in response to other agents: resistance to BCNU and Galactitol, increased sensitivity to Adriamycin, and no change to ionizing radiation. These experiments suggest that once repeated treatments with a single agent cause a tumor cell population to become more resistant, sensitivity to other agents may also change unpredictably.

KW - adriamycin

KW - astrocytoma

KW - drug resistance

KW - nitrosourea

KW - radiation

UR - http://www.scopus.com/inward/record.url?scp=0024262681&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024262681&partnerID=8YFLogxK

U2 - 10.1007/BF00173647

DO - 10.1007/BF00173647

M3 - Article

C2 - 3229942

AN - SCOPUS:0024262681

VL - 6

SP - 293

EP - 298

JO - Investigational New Drugs

JF - Investigational New Drugs

SN - 0167-6997

IS - 4

ER -