PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Nitrogen Mustard Compounds”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1976

Comparative pharmacologic study in vitro and in vivo with cyclophosphamide (NSC-26271), cyclophosphamide metabolites, and plain nitrogen mustard compounds.

This paper deals with the problem of the relative selectivity of the antitumor effect of cyclophosphamide (CP). CP and its metabolites are pharmacologically characterized by determining their chemical and biological activities in vitro and their pharmacotherapeutic properties in vivo. Of particular importance is the specificity of the cytotoxic activity (cytostatic units/mumol) in vitro and the margin of safety (therapeutic index) in vivo. The pharmacologic data reveal: a. Of the various metabolites of CP only 4-hydroxycyclophosphamide, the primary activation product, exerts a highly specific cytotoxic activity in vitro and has a wide margin of safety in vivo. b. The decisive step in toxication is the formation of the alkylating N,N-bis(2-chloroethyl)phosphorodiamidic acid after acrolein has been split off.

Acrolein↗
PubMed1978

Mutagenicity of heterocyclic nitrogen mustards (ICR compounds) in cultured mammalian cells.

The mutagenicity of six heterocylic nitrogen mustards (ICR compounds) has been determined in a cultured mammalian cell system by use of resistance to the purine analog 6-thioguanine to select for mutation induction at the hypoxanthine-guanine phosphoribosyltransferase locus in Chinese hamster ovary cells. The six compounds tested are ICR 191, 170, 292, 372, 191-OH, and 170-OH. The first four contain a single 2-chloroethyl group (nitrogen half-mustard) on the side chain and are mutagenic, with the tertiary amine types (170 and 292) 3 to 5 times more mutagenic than the secondary amine types (191 and 372). The remaining two compounds (191-OH and 170-OH) are not mutagenic, indicating that the 2-chloroethyl group is needed for mutation induction.

Cell Line↗
PubMed1976

[The influence of the N-mustard derivative "cytostasan" on pregnancy and fetal development in the rat].

This presentation describes the action of Cytostasan, a nitrogen mustard compound of benzimidazole, on reproduction and embryonic development of Wistar rats. Single doses from 20 through 100 mg/kg body weight were given intraperitoneally on the 4th, 7th, 9th, 11th or 13th day post coitum. All test animals were sacrificed on the 20th day of pregnancy. The following parameters served as a base for evaluation: the means of implantation rates, resorption rates, fetal body weights and the number of dead and living fetuses. Malformations were detected by outer inspection for gross anomalies, by means of the razor blade technique for malformations of organs and by alizarin preparations for detecting anomalies of the osseuos skeleton. All results were compared with those of an untreated control group and evaluated by statistical means. Cytostasan exerts embryotoxic and teratogenic effects in appropriate dosage. Notwithstanding the fact of giving high doses (1/2 LD 50) there is no loss of blastocysts before implantation: the number of implantation sites equals that of the control group. The resorption rate increases at all examined days of development after application of 40 mg/kg, but 20 mg/kg exert effects only on days 4, 7, and 11 p. c. There is no action on the number of living fetuses after injection of 20 mg Cytostasan/kg body weight. After application of 40 mg/kg the number of living fetuses decreases especially on the 7th, 9th, and 13th day p. c. There is a dose-dependent stunting: the fetal body weight is not reduced after a dosage of 20 mg/kg, but 40 mg/kg cause a considerable loss of weight during embryogenesis (days 9, 11, 13). It is impossible to induce stunting during blastogenesis (days 4 and 7). The observed patterns of malformation are relatively uniform: kinked tails, omphaloceles, hydronephroses, hydrocephali. Skeletal defects are absent. The results received are compared with other findings on aklylating antitumour drugs.

Abnormalities, Drug-Induced↗
PubMed1975

Influence of anti-oestrogens on the specific binding in vitro of (3H)oestradiol by cytosol of rat mammary tumours and human breast carcinomata.

The anti-oestrogenic potential of two nitrogen-mustard-containing compounds, I.C.I. 79792 and I.C.I. 85966, was studied. I.C.I. 85966 usually did not decrease specific binding of [3H]oestradiol by breast-tumour cytoplasmic proteins. I.C.I. 79792 decreased specific [3H]oestradiol binding, but not to the same extent as similar concentrations of I.C.I. 46474, diethylstilboestrol or dibutyldihydrostilboestrol.

Animals↗
PubMed1977

Inhibition of neutrophil chemotaxis by 4-hydroxycyclophosphamide.

4-Hydroxycyclophosphamide, phosphoramide mustard, and nor-nitrogen mustard are compounds considered as candidates for the biologically active, alkylating metabolite of cyclophosphamide. These compounds were tested for inhibition of chemotaxis in neutrophils from normal human donors. Of those tested, only 4-hydroxycyclophosphamide caused a significant (p less than 0.01) decrease in the chemotactic index. The chemical precursor of 4-hydroxycyclophosphamide, 4-hydroperoxycyclophosphamide, caused a barely significant (p less than 0.05) decrease; 4-ketocyclophosphamide had no effect.

Alkylating Agents↗
PubMed1975

In vivo repair of rat intestinal DNA damage by alkylating agents.

In an effort to evaluate the possible correlation of the transforming ability of the known colon carcinogens dimethylhydrazine, 3-2'-dimethyl-4-aminobiphenyl, and methylazoxymethanolacetate to damage and repair of DNA, a series of compounds known to react with DNA-nitrogen mustard, methylmethanesulfonate, and mitomycin C--were administered to rats that had been prelabeled with 3H-thymidine. The DNA of crypt and villus of the jejunum and crypt and surface cells of the large bowel were analyzed by ultracentrifugation on an alkaline sucrose gradient. All fractions suffered degradation to such an extent that essentially no undamaged DNA was detectable. This was followed by repair and an increase in size. However, in the surface cells of the colon of animals that had received a carcinogenic insult there was far less rapid repair. Since this is the site where tumors would ultimately arise these data are supportive of the hypothesis that there is a relationship between decreased repair and carcinogenicity. In view of the age related incidence of colon cancer, repair in older animals was evaluated and was found to be less than that seen in the young. Since multiple treatment with the carcinogen dimethylhydrazine is required and there is a long latent period, the effect of this treatment on repair potential was evaluated. Similar to what was seen in the older animals, these treated rats had greatly reduced capacity to repair DNA. All these observations are consistent with the hypothesis that decreased repair of DNA alterations is a concomitant of carcinogenesis.

Alkylating Agents↗
PubMed1992

The nature of cytotoxic drug-induced cell death in murine intestinal crypts.

The nature of cell death in murine small intestinal crypts caused by potentially lethal doses of four classes of cancer chemotherapeutic agents was studied. The drugs used were cytosine arabinoside, vincristine, adriamycin and nitrogen mustard. The compounds readily induced massive cell death in the proliferating compartment of the crypt. In each case, cell death was apparent within an hour, and the incidence of dead cells peaked during the following 4-8 h. By 24 h, little damage was discernible in the crypt systems. Remarkably, dead cells or dead cell fragments were phagocytosed rapidly (within about 1 h) by neighbouring healthy enterocytes. When examined by light microscopy, transmission electron microscopy and scanning electron microscopy, the dead cells showed the characteristic features of having succumbed to an apoptotic mode of cell death without any trace of cell and organelle oedema characteristic of necrosis. The study suggests that cell death by apoptosis operates even when the cells are exposed to severe pathological perturbation and that the phenomenon is not solely a process which operates in response to either physiological stimuli or to mild physical or chemical trauma.

Animals↗
PubMed1976

Biologic activity of two derivatives and six possible metabolites of cyclophosphamide (NSC-26271).

The biologic activity in terms of survival of normal hematopoietic stem, osteosarcoma, and L1210 leukemia cells was determined for the following compounds:cyclophosphamide, its derivatives isophosphamide and trophosphamide, its possible metabolites nor-nitrogen mustard, hydroxylamine mustard, 4-ketocyclophosphamide, and and acrolein, and two substitutes for its primary active metabolite 4-hydroxycyclosphamide anhydro-dimer (4-hydroxy-CP-anhydro-dimer) and 4-hydroperoxycyclophosphamide (4-hydroperoxy-CP). On a molar basis none of the compounds shows a better therapeutic ratio between osteosarcoma and bone marrow stem cells than the parent compound. The therapeutic ratio between L1210 leukemia and normal cells is slightly better for 4-hydroperoxy-CP only. It may be concluded that the conversion of 4-hydroxy-CP-anhydro-dimer and 4-hydroperoxy-CP to the primary active metabolite 4-hydroxycyclophosphamide differs quantitatively. Moreover, it appears that by the use of these precursors a better therapeutic ratio might be obtained for some malignancies but not for others.

Acrolein↗
PubMed1979

Potential antineoplastics. 4th communication: N-mustard derivatives of estrone).

The nitrogen mustards 5 and 9 are synthesized as potential mammatropic antineoplastic agents from estrone via 2--4 or 6--8, respectively. 5 and 9 show a binding affinity to the cytoplasmic estrogen receptor of the rat uterus of 1--10% compared to that of estrone. Both mustard compounds are irreversibly bound to the estrogen receptor.

Animals↗
PubMed1978

In vivo interaction between steroidal alkylating agents and oestrogen receptors in rabbit uteri.

The binding of steroidal alkylating agents to specific tissue component is necessary for the selective distribution of these compounds to their target tissues. The in vivo interaction of Estracyt or NSC-112259 with oestrogen receptors may play an important role in their action mechanism. Both Estracyt and NSC-112259 which were administered in vivo, gradually reduced the binding of [3H] oestradiol to cytoplasmic oestrogen receptor in rabbit uteri. From this, it was suggested that a negligible amount of oestradiol was released from these compounds and that the oestradiol moiety was useful as a carrier for the nitrogen mustard moiety. And it appeared that the synthesis of a new receptor protein was inhibited by the nitrogen mustard moiety, thereby causing a decrease in the cytoplasmic oestrogen receptor level.

Animals↗
PubMed1976

Potential CNS antitumor agents--phenothiazines I: Nitrogen mustard derivatives.

Four phenothiazine derivatives containing the bis(beta-chloroethyl)aminopropyl side chain were prepared and evaluated in the murine L-1210, P-388, and B-16 melanoma intraperitoneal tumor systems. Moderate P-388 activity was observed. An aminoethyl phenothiazine mustard was compared with the aminopropyl analogs and was superior in all test systems. None of the compounds tested against the murine ependymoblastoma brain tumor system was active.

Animals↗