Cyclophosphamide: Review of its mutagenicity for an assessment of potential germ cell risks

Anderson, Diana; Bishop, Jack B.; Garner, R.C.; Ostrosky‐Wegman, Patricia; Selby, Paul B.

doi:10.1016/0027-5107(95)00039-l

Cited by 259 publications

(177 citation statements)

References 216 publications

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“…It is well known that the relationship between the onset of DNA damage and the time after exposure depend on the mechanism of DNA damage and that the measured damage level is a result of equilibrium between damage infliction and repair [49]. Cyclophosphamide forms crosslinks that are translated into DNA strand breaks during excision repair [50]. Since alkylating agents do not induce ssb directly, it is important to take in account that the level of detectable DNA damage is dependent on repair rate, the half-life of AP sites and/or breaks as well as on the alkaly-lability of AP sites [46].…”

Section: Discussionmentioning

confidence: 99%

Assessment of chemotherapy‐induced DNA damage in peripheral blood leukocytes of cancer patients using the alkaline comet assay

Kopjar

Garaj‐Vrhovac

Milas

2001

Teratog Carcinog Mutagen

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The alkaline comet assay was employed to assess the pre-and post-treatment levels of in vivo DNA damage in peripheral blood leukocytes of cancer patients. During the study all patients were given antineoplastic drugs, mainly as polychemotherapy. To quantify the DNA damage, two different comet parameters were evaluated: the tail length and the tail moment. Our results indicate marked interindividual variations between baseline DNA damage in peripheral blood leukocytes recorded among cancer patients prior to the chemotherapy. After intravenous administration of various antineoplastic drugs, a significantly increased level of DNA damage in all cancer patients compared to their pre-treatment values was recorded The highest level of DNA damage was seen following administration of 5-fluorouracil, adriamycin, and cisplatin (FAP protocol). The results indicate that administration of antineoplastic drugs in standard protocols is accompanied by significant DNA damage in peripheral blood leukocytes. In order to diminish the potential risks of developing second neoplasms, a continuous biomonitoring of cancer patients after the ending of chemotherapy becomes important. Despite their limitations, present results confirm the usefulness of the alkaline comet assay as a sensitive biomarker of exposure that enables rapid and simple detection of primary DNA damage in peripheral blood leukocytes of cancer patients. Together with standard cytogenetic endpoints, the comet assay provides a powerful technique for the routine detection of critical DNA lesions produced after administration of antineoplastic drugs in the clinical settings. Teratogenesis Carcinog. Mutagen. 22:13-30, 2002.

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Section: Discussionmentioning

confidence: 99%

Assessment of chemotherapy‐induced DNA damage in peripheral blood leukocytes of cancer patients using the alkaline comet assay

Kopjar

Garaj‐Vrhovac

Milas

2001

Teratog Carcinog Mutagen

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“…Cyclophosphamide, an alkylating agent used in chemotherapy, requires metabolic activation before it can act as a mutagenic agent to promote chromosomal aberrations (Anderson et al, 1995). Vinblastine sulfate, an aneugenic agent derived from Vinca alkaloids and used here as a positive control, inhibits the polymerization of the tubulin dimer in vitro, thereby preventing cell proliferation at low concentrations (Kallio et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Micronucleus frequencies in Astyanax bimaculatus (Characidae) treated with cyclophosphamide or vinblastine sulfate

Matsumoto

Cólus

2000

Genet. Mol. Biol.

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Two known mutagenic drugs, cyclophosphamide and vinblastine sulfate, were tested using the micronucleus test in the native fish species, Astyanax bimaculatus, in order to determine which of these drugs and the doses which would be the most adequate for use as positive controls in this species. This Brazilian fish species was chosen because few toxicity studies have used native fish species and this particular species is widely consumed in various regions of Brazil. Three thousand erythrocytes per specimen were scored. Doses of 16 and 8 mg/kg body weight of cyclophosphamide and vinblastine sulfate, respectively, were the most effective in causing micronuclei. Cyclophosphamide was the most mutagenic of the two drugs and is recommended for use as a positive control in A. bimaculatus.
Duas drogas reconhecidas como mutagênicas, ciclofosfamida e vimblastina sulfato, foram avaliadas usando o teste do micronúcleo em uma espécie de peixe nativa, Astyanax bimaculatus, para detectar que droga e quais doses são as mais adequadas para serem usadas como controles positivos para esta espécie. Esta espécie de peixe brasileira foi escolhida devido à escassez de estudos toxicológicos com espécies de peixes nativos e também porque ela é amplamente consumida em algumas regiões do Brasil. Um total de 3000 eritrócitos por espécimen foram contados. As doses de 16 e 8 mg/kg de peso corporal de ciclofosfamida e de vimblastina sulfato, respectivamente, foram as mais efetivas na indução de micronúcleos. A ciclofosfamida mostrou ser o melhor agente mutagênico para ser usado como um controle positivo para Astyanax bimaculatus

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“…Male gonad evaluation requires a complete urologic examination in order to determine semen alterations due to increasing age (3,4), genital system abnormalities (e.g., varicocele, orchitis, testicular cancer, mumps) (5), influence of drugs (particularly intravenous cyclophosphamide [IV CYC]) (6)(7)(8)(9), and antisperm antibodies (10). There is, however, no systematic study in the literature assessing the overall gonad function in male SLE patients and its relevance for sperm abnormalities.…”

Section: Objective To Assess Gonad Function In Male Patients With Symentioning

confidence: 99%

Gonad evaluation in male systemic lupus erythematosus

Soares¹,

Borba²,

Bonfá³

et al. 2007

Arthritis & Rheumatism

103

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Objective. To assess gonad function in male patients with systemic lupus erythematosus (SLE).Methods. Thirty-five consecutive male patients with SLE according to the criteria of the American College of Rheumatology were prospectively evaluated for demographic and clinical features as well as previous and current treatment. Patients underwent urologic evaluation and testicular Doppler ultrasound. We obtained a hormone profile and performed a semen analysis including morphology and testing for the presence of antisperm antibodies. Patients were compared with 35 age-matched healthy controls.Results. Compared with controls, SLE patients had lower median testicular volumes in both testes, a lower median total sperm count, and a lower median total motile sperm count. The mean sperm volume and percentage of normally formed sperm were lower in SLE patients than in controls. Since all SLE patients had semen alterations, they were further subdivided into 2 groups according to the severity of these abnormalities (group 1, with teratozoospermia [n ‫؍‬ 18], and group 2, with azoospermia or teratozoospermia in combination with oligozoospermia and/or asthenozoospermia [n ‫؍‬ 17]). The frequency of treatment with intravenous cyclophosphamide (IV CYC) after the first ejaculation was higher in group 2 than in group 1. The median testicular volumes measured by ultrasound in both testicles were lower in group 2 than in group 1. Follicle-stimulating hormone levels were higher in group 2 than in group 1. The overall frequency of antisperm antibodies in SLE patients was 40%. The apparent higher frequency of antisperm antibodies in group 1 than in group 2 did not reach significance.Conclusion. SLE patients have a high frequency of sperm abnormalities associated with reduced testicular volume. Postpubertal IV CYC treatment was the major factor in potential permanent damage to the testes.

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Cyclophosphamide: Review of its mutagenicity for an assessment of potential germ cell risks

Cited by 259 publications

References 216 publications

Assessment of chemotherapy‐induced DNA damage in peripheral blood leukocytes of cancer patients using the alkaline comet assay

Assessment of chemotherapy‐induced DNA damage in peripheral blood leukocytes of cancer patients using the alkaline comet assay

Micronucleus frequencies in Astyanax bimaculatus (Characidae) treated with cyclophosphamide or vinblastine sulfate

Gonad evaluation in male systemic lupus erythematosus

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