CYCLOPHOSPHAMIDE INDUCED IN VIVO SISTER CHROMATID EXCHANGES (SCE) IN MUS MUSCULUS. I: STRAIN DIFFERENCES AND EMPIRICAL ASSOCIATION WITH RELATIVE CHROMOSOME SIZE

1982 ◽  
Vol 24 (5) ◽  
pp. 521-528 ◽  
Author(s):  
Dorothy L. Reimer ◽  
Shiva M. Singh

The inducibility of sister chromatid exchanges (SCEs) by cyclophosphamide (CP) in bone marrow cells was evaluated in vivo in the three genetic strains of mice (C3H/s, C57BL/6J, and Balb/c). Female mice (10 to 12 wks old, mean = 22.9 g, SD = 3.2 g) were administered with nine hourly injections of 214.19 mg/kg 5-Bromo-2′ deoxyuridine (BrdU) followed by 0, 0.048, 0.449, 4.585 or 46.93 mg/kg CP and 4 mg/kg colcemid. SCEs were evaluated following differential staining procedures of Perry and Wolff (1974). The base-line SCEs were similar in all strains with about ten SCEs/cell. Increasing CP concentrations yielded an increased level of SCEs. Most cells showed extensive damage in CP doses exceeding 4.55 mg/kg. No SCE evaluation was possible beyond this concentration. Strain differences were evident at every dose of CP, and Balb/c was the least susceptible strain to SCE induction. F1 hybrids involving C3H/s ♂ and Balb/c ♀ showed SCE values closer to Balb/c. Data on the association between chromosome length and frequency of SCEs are provided. They empirically establish a positive correlation (r = 0.90) between the two features. Most induced SCEs were interstitially located rather than terminally positioned on the chromosome.

1984 ◽  
Vol 26 (2) ◽  
pp. 152-157
Author(s):  
S. M. Singh ◽  
D. L. Reimer

Frequency of sister chromatid exchanges (SCE) were recorded separately for different chromosomes from bone marrow cells of female mice of the two genetic strains (C3H/S and C57BL/6J). SCEs were evaluated following different doses of 5-bromo-2′deoxyuridine (BrdU) as nine hourly i.p. injections. The SCE per cell increased with increasing BrdU doses which was slightly higher in C3H/S than in the C57BL/6J. SCEs per cell were variable at every treatment – strain combination, possibly reflecting the heterogeneous nature of the bone marrow cells. In general, there is a positive correlation between SCE per chromosome and the relative chromosome length. Total SCEs on one of the large chromosomes (most likely the X chromosome), however, are significantly higher than expected on the basis of relative length alone. Most of this increase is attributable to one of the homologues of this chromosome, which is not in synchrony with the rest of the chromosomes and may represent the late-replicating X. These results when viewed in the light of replication properties of the heterochromatinized X, suggest a direct involvement of DNA replication in SCE formation and may argue against the replication point as the sole site for the SCEs.Key words: sister chromatid exchange, BrdU, recombination, replication, X chromosome.


Genetics ◽  
1983 ◽  
Vol 105 (1) ◽  
pp. 169-179
Author(s):  
Dorothy L Reimer ◽  
Shiva M Singh

ABSTRACT In vivo cyclophosphamide (CP)-induced sister chromatid exchanges (SCEs) were evaluated in females from five genetic strains of mice (C57BL/6J, C3H/S, 129/ReJ, BALB/c and DBA/2) and their F1 hybrids. Baseline (noninduced) SCE values differ significantly among strains, 129/ReJ having the lowest and DBA/2 having the highest mean SCE per cell values. In general, the baseline SCE of a given F1 is within the range of its corresponding parental strains or near the lower parental value. Furthermore, there is a genotype-dependent increase in mean SCEs per cell with CP dose. Strain differences in SCE induction are noted particularly at the two higher CP doses (4.50 and 45.0 mg/kg). In general, F1 hybrids involving a strain with high induced SCEs and a strain with low induced SCEs exhibit mean SCE values that are closer to the value of the lower strain. F1s involving two strains with high SCEs or two strains with low SCEs yield SCEs not different from parental strains. The method of diallel cross analysis showed the order of dominance of these strains in SCE induction to be 129/ReJ BALB/c C3H/S DBA/2 C57BL/6J. These results support the involvement of predominantly nonadditive genetic factors as major gene(s) in SCE induction. In addition, involvement of random and independent events in SCE induction is suggested by the distribution of SCEs which follows a Poisson distribution.


Genetics ◽  
1982 ◽  
Vol 100 (2) ◽  
pp. 259-278
Author(s):  
Hideo Tsuji

ABSTRACT Sister chromatid exchanges (SCEs) under in vivo and in vitro conditions were examined in ganglion cells of third-instar larvae of Drosophila melanogaster (Oregon-R). In the in vivo experiment, third-instar larvae were fed on synthetic media containing 5-bromo-2′-deoxyuridine (BrdUrd). After two cell cycles, ganglia were dissected and treated with colchicine. In the in vitro experiment, the ganglia were also incubated in media containing BrdUrd for two cell cycles, and treated with colchicine. SCEs were scored in metaphase stained with Hoechst 33258 plus Giemsa. The frequencies of SCEs stayed constant in the range of 25-150 vg/ml and 0.25-2.5 vg/ml of BrdUrd in vivo and in vitro, respectively. SCEs gradually increased at higher concentrations, strongly suggesting that at least a fraction of the detected SCEs are spontaneous. The constant levels of SCE frequency were estimated, on the average, at 0.103 per cell per two cell cycles for females and 0.101 for males in vivo and at 0.096 for females and 0.091 for males in vitro. No difference was found in the SCE frequency between sexes at any of the BrdUrd concentrations. The analysis for the distribution of SCEs within chromosomes revealed an extraordinarily high proportion of the SCEs at the junctions between euchromatin and heterochromatin; the remaining SCEs were preferentially localized in the euchromatic regions of the chromosomes and in the heterochromatic Y chromosome. These results were largely inconsistent with those of Gatti et al. (1979).


2010 ◽  
Vol 2010 ◽  
pp. 1-4 ◽  
Author(s):  
Entissar S. AlSuhaibani

Aspartame (a-Laspartyl-L-phenylalanine 1-methylester) is a dipeptide low-calorie artificial sweetener that is widely used as a nonnutritive sweetener in foods and drinks. The safety of aspartame and its metabolic breakdown products (phenylalanine, aspartic acid and methanol) was investigatedin vivousing chromosomal aberration (CA) test and sister chromatid exchange (SCE) test in the bone marrow cells of mice. Swiss Albino male mice were exposed to aspartame (3.5, 35, 350 mg/kg body weight). Bone marrow cells isolated from femora were analyzed for chromosome aberrations and sister chromatid exchanges. Treatment with aspartame induced dose dependently chromosome aberrations at all concentrations while it did not induce sister chromatid exchanges. On the other hand, aspartame did not decrease the mitotic index (MI). However, statistical analysis of the results show that aspartame is not significantly genotoxic at low concentration.


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