Kinetic and morphometric responses of heterogeneous populations of NMU-induced rat mammary tumor cells to hormone and antipolyamine therapy in vivo

Andrea Manni, Scott Lancaster, Hugh English, Betty Badger, James Lynch, Laurence Demers

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The present experiments were designed to evaluate in vivo the differential sensitivity of tumor cell subpopulations to hormone and polyamine manipulations using the hormone-responsive N-nitrosomethyl-urea (NMU)-induced rat mammary tumor. NMU tumor bearing rats were randomly assigned to control, ovariectomy, α-difluoromethyl-ornithine (DFMO) administration (an inhibitor of polyamine biosynthesis), or combination treatment, and were sacrificed on day 2, 4, or 7. The proportion of different cells was estimated by morphometric analysis and their replicative activities by [3H]-thymidine autoradiography. In tumors of intact rats, the fractions of glandular, myoepithelial, and non-epithelial cells were 85.3 ± 2.2%, 4.7 ± 0.7%, and 9.9 ± 1.9%, respectively. Ovariectomy induced a similar time-dependent decline in the labelling indices of each cell type (from 5% to 1%). It also decreased the fraction of glandular cells (74.9 ± 4.5%), while increasing the fraction of myoepithelial (8.6 ± 1.9%) and non-epithelial (16.3 ± 3.2%) cells. DFMO exerted similar but more modest effects. DFMO-induced tumor regression was also inferior to that observed with ovariectomy. Combined ovariectomy and DFMO induced a faster and greater suppression of all labelling indices than the individual treatments, even though tumor regression was not superior to that produced by ovariectomy alone. Combination treatment also produced more profound morphologic changes, reducing the fraction of glandular cells to 64.4 ± 3.9% and increasing that of non-epithelial cells to 26.6 ± 4.4%. Ovariectomy and DFMO reduced height but not width of glandular cells, resulting in a modest decrease in cell volume. The combination treatment, however, significantly suppressed all three parameters. Cellular levels of polyamines were only modestly affected by the treatment used, thus raising doubts on their role as mediators, at least of ovariectomy-induced effects. Nevertheless, these results emphasize the sensitivity of different cell components of NMU tumors to combined hormone and anti-polyamine therapy with regard to kinetic and morphometric changes.

Original languageEnglish (US)
Pages (from-to)179-186
Number of pages8
JournalBreast Cancer Research and Treatment
Volume17
Issue number3
DOIs
StatePublished - Jan 1 1991

Fingerprint

Urea
Ovariectomy
Hormones
Breast Neoplasms
Ornithine
Polyamines
Population
Neoplasms
Therapeutics
Cellular Structures
Autoradiography
Cell Size
Thymidine

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Manni, Andrea ; Lancaster, Scott ; English, Hugh ; Badger, Betty ; Lynch, James ; Demers, Laurence. / Kinetic and morphometric responses of heterogeneous populations of NMU-induced rat mammary tumor cells to hormone and antipolyamine therapy in vivo. In: Breast Cancer Research and Treatment. 1991 ; Vol. 17, No. 3. pp. 179-186.
@article{1bc010a988fc443d97877d1482180aa3,
title = "Kinetic and morphometric responses of heterogeneous populations of NMU-induced rat mammary tumor cells to hormone and antipolyamine therapy in vivo",
abstract = "The present experiments were designed to evaluate in vivo the differential sensitivity of tumor cell subpopulations to hormone and polyamine manipulations using the hormone-responsive N-nitrosomethyl-urea (NMU)-induced rat mammary tumor. NMU tumor bearing rats were randomly assigned to control, ovariectomy, α-difluoromethyl-ornithine (DFMO) administration (an inhibitor of polyamine biosynthesis), or combination treatment, and were sacrificed on day 2, 4, or 7. The proportion of different cells was estimated by morphometric analysis and their replicative activities by [3H]-thymidine autoradiography. In tumors of intact rats, the fractions of glandular, myoepithelial, and non-epithelial cells were 85.3 ± 2.2{\%}, 4.7 ± 0.7{\%}, and 9.9 ± 1.9{\%}, respectively. Ovariectomy induced a similar time-dependent decline in the labelling indices of each cell type (from 5{\%} to 1{\%}). It also decreased the fraction of glandular cells (74.9 ± 4.5{\%}), while increasing the fraction of myoepithelial (8.6 ± 1.9{\%}) and non-epithelial (16.3 ± 3.2{\%}) cells. DFMO exerted similar but more modest effects. DFMO-induced tumor regression was also inferior to that observed with ovariectomy. Combined ovariectomy and DFMO induced a faster and greater suppression of all labelling indices than the individual treatments, even though tumor regression was not superior to that produced by ovariectomy alone. Combination treatment also produced more profound morphologic changes, reducing the fraction of glandular cells to 64.4 ± 3.9{\%} and increasing that of non-epithelial cells to 26.6 ± 4.4{\%}. Ovariectomy and DFMO reduced height but not width of glandular cells, resulting in a modest decrease in cell volume. The combination treatment, however, significantly suppressed all three parameters. Cellular levels of polyamines were only modestly affected by the treatment used, thus raising doubts on their role as mediators, at least of ovariectomy-induced effects. Nevertheless, these results emphasize the sensitivity of different cell components of NMU tumors to combined hormone and anti-polyamine therapy with regard to kinetic and morphometric changes.",
author = "Andrea Manni and Scott Lancaster and Hugh English and Betty Badger and James Lynch and Laurence Demers",
year = "1991",
month = "1",
day = "1",
doi = "10.1007/BF01806367",
language = "English (US)",
volume = "17",
pages = "179--186",
journal = "Breast Cancer Research and Treatment",
issn = "0167-6806",
publisher = "Springer New York",
number = "3",

}

Kinetic and morphometric responses of heterogeneous populations of NMU-induced rat mammary tumor cells to hormone and antipolyamine therapy in vivo. / Manni, Andrea; Lancaster, Scott; English, Hugh; Badger, Betty; Lynch, James; Demers, Laurence.

In: Breast Cancer Research and Treatment, Vol. 17, No. 3, 01.01.1991, p. 179-186.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Kinetic and morphometric responses of heterogeneous populations of NMU-induced rat mammary tumor cells to hormone and antipolyamine therapy in vivo

AU - Manni, Andrea

AU - Lancaster, Scott

AU - English, Hugh

AU - Badger, Betty

AU - Lynch, James

AU - Demers, Laurence

PY - 1991/1/1

Y1 - 1991/1/1

N2 - The present experiments were designed to evaluate in vivo the differential sensitivity of tumor cell subpopulations to hormone and polyamine manipulations using the hormone-responsive N-nitrosomethyl-urea (NMU)-induced rat mammary tumor. NMU tumor bearing rats were randomly assigned to control, ovariectomy, α-difluoromethyl-ornithine (DFMO) administration (an inhibitor of polyamine biosynthesis), or combination treatment, and were sacrificed on day 2, 4, or 7. The proportion of different cells was estimated by morphometric analysis and their replicative activities by [3H]-thymidine autoradiography. In tumors of intact rats, the fractions of glandular, myoepithelial, and non-epithelial cells were 85.3 ± 2.2%, 4.7 ± 0.7%, and 9.9 ± 1.9%, respectively. Ovariectomy induced a similar time-dependent decline in the labelling indices of each cell type (from 5% to 1%). It also decreased the fraction of glandular cells (74.9 ± 4.5%), while increasing the fraction of myoepithelial (8.6 ± 1.9%) and non-epithelial (16.3 ± 3.2%) cells. DFMO exerted similar but more modest effects. DFMO-induced tumor regression was also inferior to that observed with ovariectomy. Combined ovariectomy and DFMO induced a faster and greater suppression of all labelling indices than the individual treatments, even though tumor regression was not superior to that produced by ovariectomy alone. Combination treatment also produced more profound morphologic changes, reducing the fraction of glandular cells to 64.4 ± 3.9% and increasing that of non-epithelial cells to 26.6 ± 4.4%. Ovariectomy and DFMO reduced height but not width of glandular cells, resulting in a modest decrease in cell volume. The combination treatment, however, significantly suppressed all three parameters. Cellular levels of polyamines were only modestly affected by the treatment used, thus raising doubts on their role as mediators, at least of ovariectomy-induced effects. Nevertheless, these results emphasize the sensitivity of different cell components of NMU tumors to combined hormone and anti-polyamine therapy with regard to kinetic and morphometric changes.

AB - The present experiments were designed to evaluate in vivo the differential sensitivity of tumor cell subpopulations to hormone and polyamine manipulations using the hormone-responsive N-nitrosomethyl-urea (NMU)-induced rat mammary tumor. NMU tumor bearing rats were randomly assigned to control, ovariectomy, α-difluoromethyl-ornithine (DFMO) administration (an inhibitor of polyamine biosynthesis), or combination treatment, and were sacrificed on day 2, 4, or 7. The proportion of different cells was estimated by morphometric analysis and their replicative activities by [3H]-thymidine autoradiography. In tumors of intact rats, the fractions of glandular, myoepithelial, and non-epithelial cells were 85.3 ± 2.2%, 4.7 ± 0.7%, and 9.9 ± 1.9%, respectively. Ovariectomy induced a similar time-dependent decline in the labelling indices of each cell type (from 5% to 1%). It also decreased the fraction of glandular cells (74.9 ± 4.5%), while increasing the fraction of myoepithelial (8.6 ± 1.9%) and non-epithelial (16.3 ± 3.2%) cells. DFMO exerted similar but more modest effects. DFMO-induced tumor regression was also inferior to that observed with ovariectomy. Combined ovariectomy and DFMO induced a faster and greater suppression of all labelling indices than the individual treatments, even though tumor regression was not superior to that produced by ovariectomy alone. Combination treatment also produced more profound morphologic changes, reducing the fraction of glandular cells to 64.4 ± 3.9% and increasing that of non-epithelial cells to 26.6 ± 4.4%. Ovariectomy and DFMO reduced height but not width of glandular cells, resulting in a modest decrease in cell volume. The combination treatment, however, significantly suppressed all three parameters. Cellular levels of polyamines were only modestly affected by the treatment used, thus raising doubts on their role as mediators, at least of ovariectomy-induced effects. Nevertheless, these results emphasize the sensitivity of different cell components of NMU tumors to combined hormone and anti-polyamine therapy with regard to kinetic and morphometric changes.

UR - http://www.scopus.com/inward/record.url?scp=0025651289&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025651289&partnerID=8YFLogxK

U2 - 10.1007/BF01806367

DO - 10.1007/BF01806367

M3 - Article

C2 - 2039840

AN - SCOPUS:0025651289

VL - 17

SP - 179

EP - 186

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

SN - 0167-6806

IS - 3

ER -