Evaluation of cytotoxic effects of different doses of vinblastine on mouse spermatogenesis by flow cytometry

Ganesh Chandra Jagetia, H. Krishnamurthy, P. Jyothi

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The cytotoxic effects of different doses (0 to 8 mg/kg body weight) of vinblastine on mouse spermatogenesis were studied at 7 to 70 days post-treatment. First the gross changes in testicular weight were studied: the doses from 0.05 to 0.5 mg/kg body weight of vinblastine did not show any significant change in testicular weight. However, a dose of 1 mg/kg at day 21 and 28, and 2 mg/kg at all the intervals studied showed a significant decline in testicular weight (P < 0.003 and < 0.03 for 1 and 2 mg/kg, respectively). A further increase in vinblastine dose resulted in a significant decline in testis weight from 7 to 35 days post-treatment. Flow cytometric DNA content measurements were carried out in monocellular suspensions of mouse testis that revealed five quantifiable populations: elongated spermatids (HC), round spermatids (1C), spermatogonia (2C), gonial cells and primary spermatocytes synthesizing DNA (S-phase), and primary spermatocytes (4C) in the control animals. Administration of vinblastine resulted in significant changes in the relative percentages of different germ cell populations as a consequence of which the complete germ cell transformation ratio (HC:2C) declined significantly (P < 0.04) at 21 and 35 days post-treatment (1 and 2 mg/kg). The HC:2C ratio is further divided into 4C:2C, 1C:4C and 1C:2C ratios. The 4C:2C ratio (transformation of spermatogonia to primary spermatocyte) significantly declined at all the post-treatment intervals for 1 and 2 mg/kg vinblastine (P < 0.01). A significant decline in 1C:4C ratio (meiotic transformation) was observed at all the intervals for 0.5 mg/kg (P < 0.004, 0.05, 0.001 and 0.0002 at 7, 14, 21, 28 and 35 days, respectively). This decline in 1C:4C ratio continued at higher doses, i.e. 1 mg/kg (P < 0.0001) and 2 mg/kg (P < 0.0001, 0.005 and 0.0001, respectively) at 14, 21 and 28 days post-treatment. The 1C:2C ratio (spermatocytogenesis) decreased significantly for all the doses by day 14 and 35, except for 0.01 mg/kg (P < 0.04 to 0.0001). Our data suggest that doses of 0.5 mg/kg vinblastine were already cytotoxic to various germ cell populations.

Original languageEnglish
Pages (from-to)227-236
Number of pages10
JournalToxicology
Volume112
Issue number3
DOIs
Publication statusPublished - 02-09-1996
Externally publishedYes

Fingerprint

Flow cytometry
Vinblastine
Spermatogenesis
Flow Cytometry
Spermatocytes
Germ Cells
Weights and Measures
Spermatogonia
Spermatids
Cells
Testis
Body Weight
Population
DNA
S Phase
Suspensions
Animals

All Science Journal Classification (ASJC) codes

  • Toxicology

Cite this

Jagetia, Ganesh Chandra ; Krishnamurthy, H. ; Jyothi, P. / Evaluation of cytotoxic effects of different doses of vinblastine on mouse spermatogenesis by flow cytometry. In: Toxicology. 1996 ; Vol. 112, No. 3. pp. 227-236.
@article{4397ae4e508844828d348bfc4f7e72a4,
title = "Evaluation of cytotoxic effects of different doses of vinblastine on mouse spermatogenesis by flow cytometry",
abstract = "The cytotoxic effects of different doses (0 to 8 mg/kg body weight) of vinblastine on mouse spermatogenesis were studied at 7 to 70 days post-treatment. First the gross changes in testicular weight were studied: the doses from 0.05 to 0.5 mg/kg body weight of vinblastine did not show any significant change in testicular weight. However, a dose of 1 mg/kg at day 21 and 28, and 2 mg/kg at all the intervals studied showed a significant decline in testicular weight (P < 0.003 and < 0.03 for 1 and 2 mg/kg, respectively). A further increase in vinblastine dose resulted in a significant decline in testis weight from 7 to 35 days post-treatment. Flow cytometric DNA content measurements were carried out in monocellular suspensions of mouse testis that revealed five quantifiable populations: elongated spermatids (HC), round spermatids (1C), spermatogonia (2C), gonial cells and primary spermatocytes synthesizing DNA (S-phase), and primary spermatocytes (4C) in the control animals. Administration of vinblastine resulted in significant changes in the relative percentages of different germ cell populations as a consequence of which the complete germ cell transformation ratio (HC:2C) declined significantly (P < 0.04) at 21 and 35 days post-treatment (1 and 2 mg/kg). The HC:2C ratio is further divided into 4C:2C, 1C:4C and 1C:2C ratios. The 4C:2C ratio (transformation of spermatogonia to primary spermatocyte) significantly declined at all the post-treatment intervals for 1 and 2 mg/kg vinblastine (P < 0.01). A significant decline in 1C:4C ratio (meiotic transformation) was observed at all the intervals for 0.5 mg/kg (P < 0.004, 0.05, 0.001 and 0.0002 at 7, 14, 21, 28 and 35 days, respectively). This decline in 1C:4C ratio continued at higher doses, i.e. 1 mg/kg (P < 0.0001) and 2 mg/kg (P < 0.0001, 0.005 and 0.0001, respectively) at 14, 21 and 28 days post-treatment. The 1C:2C ratio (spermatocytogenesis) decreased significantly for all the doses by day 14 and 35, except for 0.01 mg/kg (P < 0.04 to 0.0001). Our data suggest that doses of 0.5 mg/kg vinblastine were already cytotoxic to various germ cell populations.",
author = "Jagetia, {Ganesh Chandra} and H. Krishnamurthy and P. Jyothi",
year = "1996",
month = "9",
day = "2",
doi = "10.1016/0300-483X(96)03402-6",
language = "English",
volume = "112",
pages = "227--236",
journal = "Toxicology",
issn = "0300-483X",
publisher = "Elsevier Ireland Ltd",
number = "3",

}

Evaluation of cytotoxic effects of different doses of vinblastine on mouse spermatogenesis by flow cytometry. / Jagetia, Ganesh Chandra; Krishnamurthy, H.; Jyothi, P.

In: Toxicology, Vol. 112, No. 3, 02.09.1996, p. 227-236.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Evaluation of cytotoxic effects of different doses of vinblastine on mouse spermatogenesis by flow cytometry

AU - Jagetia, Ganesh Chandra

AU - Krishnamurthy, H.

AU - Jyothi, P.

PY - 1996/9/2

Y1 - 1996/9/2

N2 - The cytotoxic effects of different doses (0 to 8 mg/kg body weight) of vinblastine on mouse spermatogenesis were studied at 7 to 70 days post-treatment. First the gross changes in testicular weight were studied: the doses from 0.05 to 0.5 mg/kg body weight of vinblastine did not show any significant change in testicular weight. However, a dose of 1 mg/kg at day 21 and 28, and 2 mg/kg at all the intervals studied showed a significant decline in testicular weight (P < 0.003 and < 0.03 for 1 and 2 mg/kg, respectively). A further increase in vinblastine dose resulted in a significant decline in testis weight from 7 to 35 days post-treatment. Flow cytometric DNA content measurements were carried out in monocellular suspensions of mouse testis that revealed five quantifiable populations: elongated spermatids (HC), round spermatids (1C), spermatogonia (2C), gonial cells and primary spermatocytes synthesizing DNA (S-phase), and primary spermatocytes (4C) in the control animals. Administration of vinblastine resulted in significant changes in the relative percentages of different germ cell populations as a consequence of which the complete germ cell transformation ratio (HC:2C) declined significantly (P < 0.04) at 21 and 35 days post-treatment (1 and 2 mg/kg). The HC:2C ratio is further divided into 4C:2C, 1C:4C and 1C:2C ratios. The 4C:2C ratio (transformation of spermatogonia to primary spermatocyte) significantly declined at all the post-treatment intervals for 1 and 2 mg/kg vinblastine (P < 0.01). A significant decline in 1C:4C ratio (meiotic transformation) was observed at all the intervals for 0.5 mg/kg (P < 0.004, 0.05, 0.001 and 0.0002 at 7, 14, 21, 28 and 35 days, respectively). This decline in 1C:4C ratio continued at higher doses, i.e. 1 mg/kg (P < 0.0001) and 2 mg/kg (P < 0.0001, 0.005 and 0.0001, respectively) at 14, 21 and 28 days post-treatment. The 1C:2C ratio (spermatocytogenesis) decreased significantly for all the doses by day 14 and 35, except for 0.01 mg/kg (P < 0.04 to 0.0001). Our data suggest that doses of 0.5 mg/kg vinblastine were already cytotoxic to various germ cell populations.

AB - The cytotoxic effects of different doses (0 to 8 mg/kg body weight) of vinblastine on mouse spermatogenesis were studied at 7 to 70 days post-treatment. First the gross changes in testicular weight were studied: the doses from 0.05 to 0.5 mg/kg body weight of vinblastine did not show any significant change in testicular weight. However, a dose of 1 mg/kg at day 21 and 28, and 2 mg/kg at all the intervals studied showed a significant decline in testicular weight (P < 0.003 and < 0.03 for 1 and 2 mg/kg, respectively). A further increase in vinblastine dose resulted in a significant decline in testis weight from 7 to 35 days post-treatment. Flow cytometric DNA content measurements were carried out in monocellular suspensions of mouse testis that revealed five quantifiable populations: elongated spermatids (HC), round spermatids (1C), spermatogonia (2C), gonial cells and primary spermatocytes synthesizing DNA (S-phase), and primary spermatocytes (4C) in the control animals. Administration of vinblastine resulted in significant changes in the relative percentages of different germ cell populations as a consequence of which the complete germ cell transformation ratio (HC:2C) declined significantly (P < 0.04) at 21 and 35 days post-treatment (1 and 2 mg/kg). The HC:2C ratio is further divided into 4C:2C, 1C:4C and 1C:2C ratios. The 4C:2C ratio (transformation of spermatogonia to primary spermatocyte) significantly declined at all the post-treatment intervals for 1 and 2 mg/kg vinblastine (P < 0.01). A significant decline in 1C:4C ratio (meiotic transformation) was observed at all the intervals for 0.5 mg/kg (P < 0.004, 0.05, 0.001 and 0.0002 at 7, 14, 21, 28 and 35 days, respectively). This decline in 1C:4C ratio continued at higher doses, i.e. 1 mg/kg (P < 0.0001) and 2 mg/kg (P < 0.0001, 0.005 and 0.0001, respectively) at 14, 21 and 28 days post-treatment. The 1C:2C ratio (spermatocytogenesis) decreased significantly for all the doses by day 14 and 35, except for 0.01 mg/kg (P < 0.04 to 0.0001). Our data suggest that doses of 0.5 mg/kg vinblastine were already cytotoxic to various germ cell populations.

UR - http://www.scopus.com/inward/record.url?scp=0030565499&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030565499&partnerID=8YFLogxK

U2 - 10.1016/0300-483X(96)03402-6

DO - 10.1016/0300-483X(96)03402-6

M3 - Article

C2 - 8845043

AN - SCOPUS:0030565499

VL - 112

SP - 227

EP - 236

JO - Toxicology

JF - Toxicology

SN - 0300-483X

IS - 3

ER -