PMID- 3080821
OWN - NLM
STAT- MEDLINE
DCOM- 19860304
LR  - 20190727
IS  - 0041-008X (Print)
IS  - 0041-008X (Linking)
VI  - 82
IP  - 1
DP  - 1986 Jan
TI  - Toxicity of thiotepa on mouse spermatogenesis as determined by dual-parameter 
      flow cytometry.
PG  - 151-63
AB  - Multiparameter flow cytometry (FCM) measurements were made on acridine orange 
      (AO)-stained mouse testicular cells and epididymal sperm cells to determine the 
      effects of varying dosages of thiotepa (0-5 mg/kg ip daily X 5 days) on 
      spermatogenesis at 7, 28, and 67 days after the last exposure (ALE). FCM 
      multiparameter measurements included DNA stainability vs RNA content, peak 
      amplitude vs integrated area of DNA fluorescent signal, and double-stranded DNA 
      vs single-stranded DNA. Thiotepa exhibited dramatic damaging effects on the 
      kinetics and/or cell kill of seven testicular cell types measured by 
      dual-parameter flow cytometry. At 7 days ALE, one 4N cell type, likely the 
      pachytene spermatocyte, was absent from the testes, and another was reduced by 
      about 70%. By 28 days ALE, most of the germ cells were absent from the 
      seminiferous tubules, and by 67 days ALE the testes were undergoing recovery of 
      spermatogenesis with only half of the seminiferous tubules repopulated after 
      treatment with 5.0 mg/kg. The dual parameters of DNA stainability vs RNA content 
      provided better resolution of testicular cell types into distinct populations 
      than the peak vs area processing of the green fluorescent signal of AO-stained 
      cells. Dosage of thiotepa was significantly related to percentage of sperm head 
      morphological abnormalities assayed by light microscopy. Utilizing the 
      metachromatic properties of acridine orange, FCM measurements of the amount of 
      single-stranded DNA induced within acid-stressed whole sperm or heat-stressed 
      nuclei detected alterations of chromatin structure at the same minimal effective 
      dose required to increase abnormal sperm head morphology. Epididymal sperm 
      isolated from mice exposed to some concentrations of thiotepa had an increased 
      percentage of free heads and tails. DNA in free heads denatured in situ to a 
      greater extent than DNA in intact sperm.
FAU - Evenson, D P
AU  - Evenson DP
FAU - Baer, R K
AU  - Baer RK
FAU - Jost, L K
AU  - Jost LK
FAU - Gesch, R W
AU  - Gesch RW
LA  - eng
GR  - R01ES0305/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Chromatin)
RN  - 905Z5W3GKH (Thiotepa)
SB  - IM
MH  - Animals
MH  - Body Weight/drug effects
MH  - Chromatin/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Flow Cytometry
MH  - Male
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Mice, Inbred C57BL
MH  - Organ Size/drug effects
MH  - Sperm Head/drug effects
MH  - Spermatogenesis/*drug effects
MH  - Testis/drug effects
MH  - Thiotepa/*pharmacology
EDAT- 1986/01/01 00:00
MHDA- 1986/01/01 00:01
CRDT- 1986/01/01 00:00
PHST- 1986/01/01 00:00 [pubmed]
PHST- 1986/01/01 00:01 [medline]
PHST- 1986/01/01 00:00 [entrez]
AID - 0041-008X(86)90447-3 [pii]
AID - 10.1016/0041-008x(86)90447-3 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 1986 Jan;82(1):151-63. doi: 10.1016/0041-008x(86)90447-3.