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At least 73 records · Page 4Linked to original sources
PubMed1990

In vivo effects of single or combined dietary antimutagens on mutagen-induced chromosomal aberrations.

The food components chlorophyllin, beta-carotene and alpha-linolenic acid (in its methyl ester form) were tested in Chinese hamsters for antimutagenic activity on the powerful mutagen thio-tepa. Each of these natural protective compounds inhibited by 70-85% the clastogenic effects induced by the mutagen. When 2 or 3 of these antimutagens were administered simultaneously no additive effects were observed. alpha-Linolenic acid methyl ester was the most effective antimutagen under the experimental conditions.

Animals↗
PubMed1975

Chemical induction of sperm abnormalities in mice.

The sperm of (C57BL X C3H)F1 mice were examined 1, 4, and 10 weeks after a subacute treatment with one of 25 chemicals at two or more dose levels. The fraction of sperm that were abnormal in shape was elevated above control values of 1.2-3.4% for methyl methanesulfonate, ethyl methanesulfonate, griseofulvin, benzo[a]pyrene, METEPA [tris(2-methyl-l-aziridinyl)phosphine oxide], THIO-TEPA [tris(l-aziridinyl)phosphine sulfide], mitomycin C, myleran, vinblastine sulphate, hydroxyurea, 3-methylcholanthrene, colchicine, actinomycin D, imuran, cyclophosphamide, 5-iododeoxyuridine, dichlorvos, aminopterin, and trimethylphosphate. Dimethylnitrosamine, urethane, DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane], 1,1-dimethylhydrazine, caffeine, and calcium cyclamate did not induce elevated levels of sperm abnormalities. The results suggest that sperm abnormalities might provide a rapid inexpensive mammalian screen for agents that lead to errors in the differentiation of spermatogenic stem cells in vivo and thus indicate agents which might prove to be mutagenic, teratogenic, or carcinogenic.

Animals↗
PubMed1977

Cidal and subcidal effect of triethylene thiophosphoramide on cell kinetics of human bladder carcinoma cells in vitro.

In view of increasing topical use of various chemotherapeutic agents for bladder carcinoma, an experimental study concerning the effect of triethylene thiophosphoramide (Thio-Tepa) on cell kinetics of bladder carcinoma cells was performed, working on an established cell line of human bladder carcinoma. This polyfunctional alkylating agent, which is most widely used for instillation chemotherapy of bladder carcinoma, revealed a concentration dependent cytotoxicity against the cells. DNA precursor incorporation suggested that repair mechanism occurred following subcidal dose of this compound and faulty repair took place following cidal dose. The cell cycle was prolonged after subcidal treatment, the main effect being seen in DNA synthetic phase, and the changes in the cell cycle parameters returned to the normal within 2 cell cycle time. Repeated treatment with subcidal dose at an interval of 48 hr led to more extensive changes in the cell cycle as compared with that of single dose. Repeated exposures to subcidal dose, however, did not show any differences in the growth curves from those of the controls.

Cell Division↗
PubMed1978

Postoperative irradiation and chemotherapy in patients with advanced ovarian cancer.

Two groups of patients with stage III ovarian carcinoma were selected for a randomized clinical trial. The first group consisted of 157 patients who had radical surgery at their first laparotomy, the second group consisted of 145 patients with inoperable disease. The aim of the trial was to compare the results of maximum external megavoltage irradiation, 5 000 rads, to a large abdominal field, with the results of a reduced dose, 3 000 rads, immediately followed by chemotherapy with an alkylating agent (Thio-tepa). In none of the groups, did maximum radiotherapy prove superior to the schedule of a reduced dose combined with chemotherapy. The less costly and time saving combined treatment was better tolerated than irradiation alone. Histological tumour type did not influence the prognosis in these advanced cases where spread was found outside the true pelvis.

Clinical Trials as Topic↗
PubMed1975

Mesonephric carcinoma of the female urethra.

Mesonephric carcinoma of the female urethra is rare arising from vestiges of the Wolffian duct and is particularly of gynaecological or urological interest. It has been treated once successfully by radical anterior pelvic exenteration. By more conservative methods of treatment such as transurethral resections, radiation or topical application of thio-tepa it is poorly controlled. The diagnosis is established by a histological pattern reminiscent of the mesonephros.

Female↗
PubMed1992

[High-dose adjuvant chemotherapy with peripheral blood stem cell transplantation for breast cancer with poor prognosis--a pilot study].

Three patients with breast cancer with poor prognosis were treated with high-dose chemotherapy (HD-CT) and peripheral blood stem cell transplantation (PBSCT) as adjuvant treatment. After radical mastectomy, the consolidation chemotherapy with Adriamycin 50 mg/m2, Cyclophosphamide 1,000 mg/m2, Vincristine 1.0 mg/m2 and Methotrexate 200 mg/m2 with Leucovorin rescue was started. Recombinant human granulocyte colony stimulating factor (rhG-CSF) was also added for early recovery from myelosuppression. This combination chemotherapy was given every 3 weeks for 3 courses, and after the 2nd and 3rd courses, peripheral blood stem cells (PBSC) were collected and cryopreserved. HD-CT with Cyclophosphamide 2,000 mg/m2/day, Thio-TEPA 200 mg/m2/day, and Etoposide 300 mg/m2/day, were administered for 3 consecutive days, and after 48 hours of last doses, frozen-thawed PBSC (6.4-8.9 x 10(4)/kg of CFU-GM) were administered. rhG-CSF was also added. HD-CT and PBSCT were well tolerated, recovery from myelosuppression of the HD-CT was very quick and no serious side effects were observed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1978

[Effect of age on the sensitivity of mouse spermatogonia to mutagenic action].

Male BALB/c mice were whole body exposed to 0, 100, 200 or 300 R of X-rays or were given an i.p. injection of 5 mg/kg of thio-TEPA at 3 months or at 12 months of age. One hundred days after treatment the testes were examined for the presence of reciprocal translocations induced in spermatogonia and detectable in the dividing spermatocytes. Our results show that ages does not influence the yield of scorable chromosome rearrangements.

Aging↗
PubMed1992

[Preliminary studies of the relationship between micronucleus formation and cell cycle. IV. Micronucleus formation induced by chemical mutagens at G0, G1, S and G2 phases of human lymphocytes].

In this paper the authors studied quantitatively the micronucleus formation at various phases of interphase in human lymphocytes induced by chemical mutagens by means of control of cell culture intervals, autoradiography and block of metaphase cells etc. The results show that mutagenic anti-tumor drugs: bimolane (treatment in vitro) and thio-tepa etc. (treatment in vivo) can induce micronucleus formation at various phases of interphase in lymphocytes. The frequency of micronucleus (MNF) induced at G1 phase is significantly higher than that at G0 and G2 phase. The MNF at S phase of cells is obviously lower than at G1. This result suggests that most of the micronucleated cells at G1 phase do not enter S phase and micronucleus rarely form at S phase of cells.

Adolescent↗
PubMed1991

Therapeutic analysis of melphalan-resistant human rhabdomyosarcoma xenograft TE-671 MR.

Investigations with the melphalan-resistant human rhabdomyosarcoma xenograft TE-671 MR were carried out to identify patterns of cross-resistance and collateral sensitivity and to define the mechanism(s) mediating melphalan resistance. TE-671 MR was cross-resistant to thio-TEPA, mitomycin, vincristine, and cisplatin, and partially resistant to chlorambucil and cyclophosphamide. TE-671 MR and the parent line TE-671 were both resistant to 1,3-bis(2-chloroethyl)-nitrosourea and expressed similar levels of O6-alkylguanine-DNA alkyltransferase. TE-671 MR retained full sensitivity to actinomycin D and demonstrated enhanced sensitivity to VP-16 compared to TE-671. Treatment of TE-671 MR with melphalan plus VP-16 resulted in greater than additive growth delays. The frequency of hypoxic regions was similar in TE-671 MR and TE-671, respectively. Measurement of tumor-to-plasma levels at 180 min following i.p. administration of melphalan at 0.5 of the 10% lethal dosage showed mean tumor-to-plasma ratios of 3.81 in TE-671 MR and 7.38 in TE-671, respectively. The lower drug levels in TE-671 MR may be contributing to the resistance to melphalan and thus indicate the need for further studies to define the reasons for these differences in tumor drug level.

Animals↗
PubMed1991

[Combination therapy of CPT-11, a camptothecin derivative, with various antitumor drugs against L 1210 leukemia].

Antitumor effect of CPT-11 in combination with cyclophosphamide (CY), nimustin hydrochloride (AC-NU), thio-TEPA (TESPA), methotrexate (MTX), 5-fluorouracil (5-FU), cytosine arabinoside (ara-C), thioinosine (6-MPR), adriamycin (ADM), bleomycin (BLM), mitomycin C (MMC), actinomycin D (ACT-D), vincristine sulfate (VCR), etoposide (VP-16) or cisplatin (CDDP) against L 1210 murine leukemia was investigated. The combination treatment of CPT-11 with CY, ACNU, ADM, CDDP, TESPA and ACT-D showed synergistic effects and significantly prolonged the survival time of L 1210-inoculated mice compared with CPT-11 alone or antitumor drug alone. Although the combination with 5-FU, 6-MPR, VP-16, MMC or VCR had synergistic effect for some schedules exceptionally with ara-C, MTX or BLM had slight synergistic effect against L 1210.

Animals↗
PubMed1977

Mutagenicity of cancer chemotherapeutic agents in the Salmonella/microsome test.

Seventeen cancer chemotherapeutic agents were tested for their ability to mutate Salmonella typhimurium tester strains in the Salmonella/microsome mutagenicity test. There was a high correlation between the mutagenicity and carcinogenicity of a given agent. Carcinogens positive in the test were Adriamycin, daunomycin, 1-propanol-3,3'-iminodimethanesulfonate, cyclophosphamide, isophosphamide, hycanthone, chlornaphazin, nitrogen mustard, uracil mustard, melphalan, and thio-tepa. Two carcinogesn, actinomycin D and bleomycin, were not detected as mutagens. The presumptive noncarcinogen, methotrexate, was negative in the test. Tilorone and 6-mercaptopurine, tentatively classified as noncarcinogens, were mutagenic. The carcinogenicity of cis-dichlorodiammineplatinum(II), which was positive in the test, has not been determined.

2-Naphthylamine↗
PubMed1978

[Metastasis to the lymph nodes as an index of the effectiveness of preoperative endolymphatic polychemotherapy of cervix cancer].

Ninety eight patients with cervical cancer were subjected to endolymphatic chemotherapy with multiple cytostatic drugs to affect metastatic lymph nodes. A comcentrated mixture of chemotherapeutic drugs (total amount about 20 ml) was injected into plantar lymph vessels, an interval being 10-14 days. The combinations and dosage of the drugs were as follows: thio-TEPA (100-150 mg) or cyclophosphamid (1000-2000 mg)+methotrexate (100 mg)+5-fluorouracil (1000-1500 mg). Subsequently, 76 patients underwent an extended extirpation of the uterus with adnexa, and their lymph-nodes were studied morphologically. It was found that the number of metastases into the lymphnodes was considerably less than it had been expected. Of 45 patients with the disease stage II metastases have been found only in 3 cases (7%). Of 24 patients with cancer stage III the lymphnodes were involved in 4 cases (16.6%). According to the literature data metastatic involvement of the lymphnodes is on an average encountered in 36% for stage II and in 51% - for stage III.

Clinical Trials as Topic↗
PubMed1975

[Chemotherapy of patients with recurring malignant tumors of the ovaries].

The results of treatment in 59 patients with recurrent malignant ovarian tumors, using three chemotherapeutic drugs: thio-TEPA, cyclophosphane and a drug from the sym.-triazine (No31) group are analysed. The effect of these substances was estimated comparatively. The frequency of remissions proved to be practically similar. However, there was noted a tendency toward greater duration of remissions with the drug No 31 chemotherapy.

Adult↗
PubMedDate not supplied

[Study of the cytogenetic activity of radioprotectors in a human lymphocyte culture. II].

Action of certain radioprotectors: 2-mercaptoethylamine HCl (MEA), cysteine HCl, 2-aminoethylsothiouronium (AET), dithiol 2,3-dimercaptopropansulphate Na (unithiol), aminopropylaminoethylthiophosphoric acid (gammaphos), cystaphos and 5-metoxytriptamine (mexamine) was studied as applied to human chromosome aberrations induced with thio-TEPA. It was shown that with an increase in thioTEPA and protectors concentrations their effect grows.

5-Methoxytryptamine↗
PubMed1975

[The mutagenic effect of thioTEPA in laboratory mice. IV. The influence of genotype and sex on the frequency of induced chromosome aberrations in bone marrow cells].

In bone marrow cells of eleven genotypes of mice strain and sex variations in sensitivity to cytogenetic effect of thio-TEPA were studied. Strains 101/H, C57BL/6 and A/Sn were the more sensitive and F1 (CBAXC57BL/6) and F1 (C3HX101) were the more resistant to induction of chromosome damages. The rate of induced chromosome aberrations was correlated with the level of spontaneous chromosome damages in bone marrow cells (r=+/-0,893+/-0,02). From all strains males were more mutable than females. It is recommended to use C57BL/6 strain of mice male for genetic tests of chemicals by cytogenetic methods in vivo.

Animals↗
PubMed1975

[The mutagenic effect of thioTEPA in laboratory mice. V. The influence of female genotype on the realization of dominant lethal mutations induced in male spermatids].

Hybrid male mice (F1 males derived from the cross DBA/2 X AKR) were injected intraperitoneally with thio-TEPA at a 2 mg/kg dose. The mutagenic effect was determined from the frequency of dominant lethal mutations induced in spermatids of males. The malles were mated during the second and the third week after the injection to females of the strains C57BL/6, CBA/lac and to the F1 hybrid females derived from the cross CBA X C57BL/6 differing in the frequency of spontaneous and induced aberrations in bone marrow cells. In the course of investigation of pregnant C57BL/6 females, F1 (CBA X C57BL/6) and CBA/Lac females the frequency of dominant lethals induced in late spermatidis was established to be 63.4, 54.0and 37.9% respectively. The differences were interpreted as the evidence of different rates of recovery of a certain proportion of premutational lesions of the chromosomes of sperms in fertilized eggcells of female mice. No significant differences between the groups of females were observed in case of the treatment of early spermatids. It is established that the F1 hybrids derived from the cross DBA/2X XAKR are characterized by a high mutability.

Animals↗