In vivo effects of 5-fluorouracil and ftorafur [1-(tetrahydrofuran-2-yl)-5-fluorouracil] on murine mammary tumors and small intestine

M. G. Pallavicini, A. M. Cohen, L. A. Dethlefsen, Joe Gray

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The in vivo anti-tumor and toxic effects of ftorafur (FT) and 5-fluorouracil (FU) were studied in the C3H mouse. On a molar basis, FU was two to three times more potent than FT with respect to growth inhibition of murine mammary adenocarcinomas. However, FT produced less host toxicity than FU when both drugs were compared at dose levels which produced equivalent anti-tumor effects. The differences between FT and FU with respect to tumor growth inhibition and host toxicity were reflected in their ability to suppress deoxyuridine incorporation into tumor cell and intestinal DNA, respectively. Flow cytometry (FCM) studies indicated that FT and FU were capable of producing pertubations in the DNA distribution of tumor cells. Both drugs induced an initial accumulation of cells in S phase following their administration at equivalent anti-tumor dose levels. At later intervals, an apparent block of cell progression at the G1/S boundary was observed. Drug-induced perturbations in the DNA distribution of tumor cells as detected by FCM correlated with results obtained by classical autoradiographic techniques using tritiated thymidine. Both procedures showed that tumor cells were capable of moving through S phase even in the presence of an apparently near complete inhibition of deoxyuridine incorporation into DNA. That such cells were, in fact, capable of synthesizing DNA at moderate rates was shown by their ability to incorporate 32P into DNA. The possible relationship of these findings to the therapeutic and toxic activities of FT and FU is discussed.

Original languageEnglish (US)
Pages (from-to)177-189
Number of pages13
JournalCell and Tissue Kinetics
Volume12
Issue number2
StatePublished - 1979
Externally publishedYes

Fingerprint

Tegafur
Fluorouracil
Small Intestine
Breast Neoplasms
DNA
Neoplasms
Deoxyuridine
Poisons
S Phase
Flow Cytometry
Pharmaceutical Preparations
tetrahydrofuran
Inbred C3H Mouse
Growth
Thymidine
Adenocarcinoma
Breast

ASJC Scopus subject areas

  • Cell Biology

Cite this

In vivo effects of 5-fluorouracil and ftorafur [1-(tetrahydrofuran-2-yl)-5-fluorouracil] on murine mammary tumors and small intestine. / Pallavicini, M. G.; Cohen, A. M.; Dethlefsen, L. A.; Gray, Joe.

In: Cell and Tissue Kinetics, Vol. 12, No. 2, 1979, p. 177-189.

Research output: Contribution to journalArticle

@article{56520d0aea4b4d6088b15274fbbbea35,
title = "In vivo effects of 5-fluorouracil and ftorafur [1-(tetrahydrofuran-2-yl)-5-fluorouracil] on murine mammary tumors and small intestine",
abstract = "The in vivo anti-tumor and toxic effects of ftorafur (FT) and 5-fluorouracil (FU) were studied in the C3H mouse. On a molar basis, FU was two to three times more potent than FT with respect to growth inhibition of murine mammary adenocarcinomas. However, FT produced less host toxicity than FU when both drugs were compared at dose levels which produced equivalent anti-tumor effects. The differences between FT and FU with respect to tumor growth inhibition and host toxicity were reflected in their ability to suppress deoxyuridine incorporation into tumor cell and intestinal DNA, respectively. Flow cytometry (FCM) studies indicated that FT and FU were capable of producing pertubations in the DNA distribution of tumor cells. Both drugs induced an initial accumulation of cells in S phase following their administration at equivalent anti-tumor dose levels. At later intervals, an apparent block of cell progression at the G1/S boundary was observed. Drug-induced perturbations in the DNA distribution of tumor cells as detected by FCM correlated with results obtained by classical autoradiographic techniques using tritiated thymidine. Both procedures showed that tumor cells were capable of moving through S phase even in the presence of an apparently near complete inhibition of deoxyuridine incorporation into DNA. That such cells were, in fact, capable of synthesizing DNA at moderate rates was shown by their ability to incorporate 32P into DNA. The possible relationship of these findings to the therapeutic and toxic activities of FT and FU is discussed.",
author = "Pallavicini, {M. G.} and Cohen, {A. M.} and Dethlefsen, {L. A.} and Joe Gray",
year = "1979",
language = "English (US)",
volume = "12",
pages = "177--189",
journal = "Cell Proliferation",
issn = "0960-7722",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - In vivo effects of 5-fluorouracil and ftorafur [1-(tetrahydrofuran-2-yl)-5-fluorouracil] on murine mammary tumors and small intestine

AU - Pallavicini, M. G.

AU - Cohen, A. M.

AU - Dethlefsen, L. A.

AU - Gray, Joe

PY - 1979

Y1 - 1979

N2 - The in vivo anti-tumor and toxic effects of ftorafur (FT) and 5-fluorouracil (FU) were studied in the C3H mouse. On a molar basis, FU was two to three times more potent than FT with respect to growth inhibition of murine mammary adenocarcinomas. However, FT produced less host toxicity than FU when both drugs were compared at dose levels which produced equivalent anti-tumor effects. The differences between FT and FU with respect to tumor growth inhibition and host toxicity were reflected in their ability to suppress deoxyuridine incorporation into tumor cell and intestinal DNA, respectively. Flow cytometry (FCM) studies indicated that FT and FU were capable of producing pertubations in the DNA distribution of tumor cells. Both drugs induced an initial accumulation of cells in S phase following their administration at equivalent anti-tumor dose levels. At later intervals, an apparent block of cell progression at the G1/S boundary was observed. Drug-induced perturbations in the DNA distribution of tumor cells as detected by FCM correlated with results obtained by classical autoradiographic techniques using tritiated thymidine. Both procedures showed that tumor cells were capable of moving through S phase even in the presence of an apparently near complete inhibition of deoxyuridine incorporation into DNA. That such cells were, in fact, capable of synthesizing DNA at moderate rates was shown by their ability to incorporate 32P into DNA. The possible relationship of these findings to the therapeutic and toxic activities of FT and FU is discussed.

AB - The in vivo anti-tumor and toxic effects of ftorafur (FT) and 5-fluorouracil (FU) were studied in the C3H mouse. On a molar basis, FU was two to three times more potent than FT with respect to growth inhibition of murine mammary adenocarcinomas. However, FT produced less host toxicity than FU when both drugs were compared at dose levels which produced equivalent anti-tumor effects. The differences between FT and FU with respect to tumor growth inhibition and host toxicity were reflected in their ability to suppress deoxyuridine incorporation into tumor cell and intestinal DNA, respectively. Flow cytometry (FCM) studies indicated that FT and FU were capable of producing pertubations in the DNA distribution of tumor cells. Both drugs induced an initial accumulation of cells in S phase following their administration at equivalent anti-tumor dose levels. At later intervals, an apparent block of cell progression at the G1/S boundary was observed. Drug-induced perturbations in the DNA distribution of tumor cells as detected by FCM correlated with results obtained by classical autoradiographic techniques using tritiated thymidine. Both procedures showed that tumor cells were capable of moving through S phase even in the presence of an apparently near complete inhibition of deoxyuridine incorporation into DNA. That such cells were, in fact, capable of synthesizing DNA at moderate rates was shown by their ability to incorporate 32P into DNA. The possible relationship of these findings to the therapeutic and toxic activities of FT and FU is discussed.

UR - http://www.scopus.com/inward/record.url?scp=0018740849&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0018740849&partnerID=8YFLogxK

M3 - Article

C2 - 371813

AN - SCOPUS:0018740849

VL - 12

SP - 177

EP - 189

JO - Cell Proliferation

JF - Cell Proliferation

SN - 0960-7722

IS - 2

ER -