Dominant lethal and heritable translocation tests with chlorambucil and melphalan in male mice

Generoso, W.M.; Witt, Kristine L.; Cain, K.T.; Hughes, L.A.; Cacheiro, N.L.A.; Lockhart, Ann-Marie; Shelby, Michael D.

doi:10.1016/0165-1218(95)90052-7

Cited by 36 publications

(23 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…There are a lot of studies on genotoxicity of metabolities of ASP (Austin et al, 1992;Brook and Chandley, 1985;Generoso et al, 1995;Sargentini and Smith, 1986). Shephard et al (1991) reported that ASP has a weak mutagenic effect in Ames test after nitrosation.…”

Section: Discussionmentioning

confidence: 99%

Genotoxicity of Aspartame

Rencüzoğulları

Tüylü

Topaktaş

et al. 2004

Drug and Chemical Toxicology

View full text Add to dashboard Cite

In the present study, the genotoxic effects of the low-calorie sweetener aspartame (ASP), which is a dipeptide derivative, was investigated using chromosome aberration (CA) test, sister chromatid exchange (SCE) test, micronucleus test in human lymphocytes and also Ames/Salmonella/ microsome test. ASP induced CAs at all concentrations (500, 1000 and 2000 mg/ml) and treatment periods (24 and 48 h) dosedependently, while it did not induce SCEs. On the other hand, ASP decreased the replication index (RI) only at the highest concentration for 48 h treatment period. However, ASP decreased the mitotic index (MI) at all concentrations and treatment periods dose-dependently. In addition, ASP induced micronuclei at the highest * Correspondence: Dr. Eyyüp Rencüzogulları, Biology Department, Faculty of Arts and Sciences, Ç ukurova University, 01330 Adana, Turkey; Fax: +90-3223386070; E-mail: reyyup@mail.cu. edu.tr. www.dekker.com concentrations only. This induction was also dose-dependent for 48 hours treatment period. ASP was not mutagenic for Salmonella typhimurium TA98 and TA100 strains in the absence and presence of S9 mix.

show abstract

Section: Discussionmentioning

confidence: 99%

Genotoxicity of Aspartame

Rencüzoğulları

Tüylü

Topaktaş

et al. 2004

Drug and Chemical Toxicology

View full text Add to dashboard Cite

show abstract

“…7 It can also induce dominant lethal mutation and heritable translocations in postmeiotic germ cells, particularly in early-mid spermatids. 8 Fludarabine is a purine analogue. However, little is known about it in relation to gonadotoxicity.…”

Section: Discussionmentioning

confidence: 99%

“…When data of individual patients were analysed prior to BMT, only four had LCI with elevated LH levels: three patients (1,6,7) had compensated type (high LH and elevated T levels) and one patient (31) had frank LCI (elevated LH and low T levels). However, another three patients (8,12, 29) had low T with normal LH levels. Post-transplant, only 4/28 had low T levels (8, 21,27,28).…”

Section: Nonmyeloablative Transplantation C Kyriacou Et Almentioning

confidence: 99%

Germ cell damage and Leydig cell insufficiency in recipients of nonmyeloablative transplantation for haematological malignancies

Kyriacou

Kottaridis

Eliahoo

et al. 2003

Bone Marrow Transplant

View full text Add to dashboard Cite

Summary:Most bone marrow transplant recipients are infertile due to reversible or irreversible testicular failure. However, little is known about the gonadotoxic potential of the newly introduced nonmyeloablative transplants. We undertook a 24-month longitudinal study in a cohort of 32 recipients of nonmyeloablative transplantation to test whether the combined regimen of fludarabine, melphalan and CAMPATH-1H can induce damage to germ cell (GC) and Leydig cell (LC) compartments. Testicular function was assessed immediately prior to transplantation and at four time points post-transplant to compare hormonal levels before and after the procedure. Two other groups treated with BEAM-and TBI-related regimes were also included in the study group for comparative purposes. GC function was assessed by measuring basal serum follicle stimulating hormone (FSH). LC function was assessed by measuring basal luteinising hormone (LH) and testosterone (T) levels. LC reserve was assessed by measuring the T/LH ratio. As a group, patients who received a non myeloablative transplant sustained severe damage to the GC compartment, as evident from a substantial elevation in the FSH level post-transplant (12 IU/l vs 18.4 IU/l, Po0.001). Similar to the GC injury, patients as a group sustained significant damage to the LC compartment following the transplant (5.4 IU/l vs 9.6 IU/ l, Po0.001). In general, patients had reduced LC reserve post-BMT, as evident from a diminished T/LH ratio (2.6 pretransplant vs 1.6 post-transplant P ¼ 0.05). Patients who received a nonmyeloablative transplant had a similar effect on the GC and LC compartments compared to those who had a BEAM autograft. On the other hand, patients who received a TBI-based transplant sustained more damage to their GC and LC compartments compared to those who received a nonmyeloblative transplant; however, this was not statistically significant (P ¼ 0.09). Our data suggest that this type of regimen is potentially gonadotoxic and consideration should be given to fertility counselling and testosterone replacement therapy posttransplant.

show abstract

“…[16][17][18] The full mutagenic potential is realised in Salmonella typhimurium after metabolic activation, principally by cytochromes P-450. 19 The induction of micronuclei, sister chromatid exchanges, chromosome aberrations, 20 specific-locus mutations, 21 dominant lethal mutations and inheritable translocations in post-meiotic germ cells in mice 22 observed. In vivo data on melphalan toxicity modification by WR-2721 [23][24][25] prompted us to evaluate the modulating effect of amifostine with different genetic endpoints, in various cellular systems.…”

Section: Introductionmentioning

confidence: 99%