Toxicology
SCSA Animal Data
Mice
Triethylmelamine (TEM). SCSA data obtained on fresh sperm were highly correlated with measurements of aliquots of the same samples collected over 44 weeks, frozen, and measured on the same day (SD of DFI, 0.88 and DFI 0.93, p<0.001). SCSA data remained abnormal at 44 weeks after triethylenemelamine (TEM) dosage suggesting that the abnormalities, present long after the initial toxic response, may be a result of mutation (Evenson, Baer and Jost, 1989). SCSA data and sperm head morphology abnormalities were highly correlated (0.87- 0.93, p<0.001) with dose of TEM and with each other.
Evenson DP, Baer RK, Jost LK.Long-term effects of triethylenemelamine exposure on mouse testis cells and sperm chromatin structure assayed by flow cytometry. Environ Mol Mutagen. 1989;14(2):79-89.
Ethylnitrosourea. Groups of mice received daily exposures ranging from 0 to 7 mg/kg body weight for five days and were killed 28 days later. Body weight were un-affected by the chemical exposure while the testicular weights were reduced by about 50%. Abnormal chromatin/DNA was found in a dose-response relationship.
Evenson DP, Higgins PJ, Grueneberg D, Ballachey BE. Flow cytometric analysis of mouse spermatogenic function following exposure to ethylnitrosourea. Cytometry. 1985 May;6(3):238-53.
Hydroxyurea High doses of hydroxyurea (200mg/kg) given to mice intraperitoneally daily for 5 d caused reduction in testicular weight of mice. Indications of abnormal chromatin structure were seen in an increased frequency of vas deferens sperm on days 27 and 33 after the last exposure.
Evenson DP, Jost LK.Hydroxyurea exposure alters mouse testicular kinetics and sperm chromatin structure. Cell Prolif. 1993 Mar;26(2):147-59.
Mice were exposed to varying doses of thiotepa (0 – 5 mg/kg) ip daily for five days) on spermatogenesis at 7, 28 and 67 days after last exposure. Thiotepa exhibited dramatic damaging effects on the kinetics and/or cell kill of seven testicular cell types. Doses of thiotepa were significantly related to percentage of sperm head morphological abnormalities. Negative effects on sperm chromatin were found at the lowest thiotepa dosage.
Evenson DP, Baer RK, Jost LK, Gesch RW.Toxicity of thiotepa on mouse spermatogenesis as determined by dual-parameter flow cytometry. Toxicol Appl Pharmacol. 1986 Jan;82(1):151-63.
Methyl methane sulfonate (MMS). Epididymal DNA damage by exposure to MMS was detected three days post injection (dpi) (and likely occurring earlier), however, but dominant lethal mutations were not detected until 8 dpi mice were bred (Evenson et al 1993). Therefore, the SCSA was apparently detecting molecular lesions days before MMS caused sufficient chromosome damage to become lethal to the developing embryo. In a similar vein, bull testes exposed to elevated temperatures caused DNA damage detectable by the SCSA at three days post heat while alterations in sperm morphology/morphometry were not detected until 12 days post heat exposure (Fig. 3) (Karabinus, Vogler, Saacke and Evenson, 1997).
Evenson DP, Jost LK, Baer RK.Effects of methyl methanesulfonate on mouse sperm chromatin structure and testicular cell kinetics. Environ Mol Mutagen. 1993;21(2):144-53.
X-radiation. The studies on effects of X-rays to mouse testes showed that the SCSA was the most sensitive assay for low dose (12 -25 rads) radiation damage. It is of interest that the X-ray damage was detected in epididymal sperm 40 days after treatment; thus, the damage done to spermatocytes persisted into epididymal sperm (Sailer, et al 1995).