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A Begleiter

Publications and source records attributed to A Begleiter.

At least 55 records · Page 3Linked to original sources
PubMed1990

Uptake and binding of 3'-(3-cyano-4-morpholinyl)-3'-deaminoadriamycin and 3'-(4-morpholinyl)-3'-deaminoadriamycin in L5178Y lymphoblasts in vitro.

3'-(3-Cyano-4-morpholinyl)-3'-deaminoadriamycin (CMA) and 3'-(4-morpholinyl)-3'-deaminoadriamycin (MA) are analogues of Adriamycin, with altered cytotoxic activity. CMA is 100- to 1500-fold more cytotoxic than Adriamycin and possesses unique DNA crosslinking activity. Intact MA does not crosslink DNA and has a cytotoxicity equivalent to Adriamycin, but it retains its activity in anthracycline-resistant cells. In this study, uptake and binding of [3H]CMA and [3H]MA in L5178Y lymphoblasts were examined. Both CMA and MA were rapidly taken up by cells at 37 degrees C and concentrated almost exclusively in the nucleus. All of the intracellular MA was TCA-soluble, but only 45% of this drug effluxed from the cells by 4 hr. More than 50% of CMA in the cells was TCA-insoluble, and approximately 40% effluxed from the cells by 4 hr through loss of the TCA-soluble fraction. CMA differed from other alkylating agents in that more than 97% of the bound drug was associated with DNA. The bound drug was partially lost from the DNA by a process that may have involved DNA repair.

Animals↗
PubMed1989

Characterization of the DNA-DNA cross-linking activity of 3'-(3-cyano-4-morpholinyl)-3'-deaminoadriamycin.

3'-(3-Cyano-4-morpholinyl)-3'-deaminoadriamycin (CMA) is a highly potent analogue of the antitumor agent, Adriamycin (ADR), being up to 1500 times more cytotoxic both in vivo and in vitro. In contrast to ADR, CMA, and 5-imino-3'-(3-cyano-4-morpholinyl)-3'-deaminoadriamycin (ICMA) have been shown to possess alkylating activity, as seen by their ability to produce DNA-DNA cross-links in human and murine tumor cells and in isolated lambda-phage DNA. We have compared the pharmacological activities of CMA, ICMA, and the alkylating agent, chlorambucil (CHL), in order to determine the roles of intercalation, the quinone ring, and DNA base composition, in cross-linking by CMA. CMA was 27-and 1000-fold more active than ICMA and CHL, respectively, in cross-linking DNA in L5178Y cells. In addition, the maximum level of cross-linking in L5178Y cells was reached more rapidly with CMA than with CHL, and the CMA cross-links were removed faster and more efficiently by these cells. CMA was 26- and 450-fold more active than ICMA and CHL, respectively, in producing DNA cross-links in isolated lambda-phage DNA. In contrast, the alkylating activity of CMA was only 6-fold greater than CHL, as measured by the ability of the drugs to bind to the nucleophile, p-nitrobenzyl pyridine. CMA was a better DNA intercalator than ICMA, whereas CHL did not intercalate. In addition, the intercalating agent, ethidium bromide, inhibited the cross-linking activity of CMA, but not that of CHL, suggesting that intercalation contributed to the cross-linking activity of CMA. CMA produced an increasing level of cross-linking, but showed no difference in intercalation, with isolated DNA of increasing G-C content, suggesting a preference for alkylating G-C bases. Both the cross-linking and intercalating, but not the alkylating, activities of CMA and ICMA were decreased by the reducing agent, sodium borohydride, providing additional evidence that the intercalative interaction of the ADR analogues with DNA contributes to their DNA cross-linking activity. Thus, alterations to the quinone group may effect the intercalating activity of these analogues and may contribute to the difference in cross-linking activity between CMA and ICMA.

Alkylation↗
PubMed1989

Increased sensitivity of quinone resistant cells to mitomycin C.

L5178Y cells resistant to the model quinone antitumor agent, hydrolyzed benzoquinone mustard, were four-fold more sensitive to mitomycin C compared to parental cells. Mitomycin C also produced increased DNA-DNA crosslinking in these cells compared to parental L5178Y cells, but did not induce DNA double strand breaks in either cell line. The resistant cells have a 24-fold increased level of DT-diaphorase activity, an enzyme that produces two electron reduction of quinone groups. Dicoumarol, an inhibitor of DT-diaphorase, significantly inhibited crosslinking and cytotoxicity by mitomycin C in the quinone resistant cells. These findings suggest that DNA-DNA cross-linking may be a major contributor to mitomycin C cytotoxic activity in L5178Y cells, and that the hydroquinone of mitomycin C may play a major role in the crosslinking activity of this agent.

Animals↗
PubMed1988

Enhanced cytotoxicity and inhibition of DNA damage repair in irradiated murine L5178Y lymphoblasts and human chronic lymphocytic leukemia cells treated with 2'-deoxycoformycin and deoxyadenosine in vitro.

The effects of irradiation were evaluated in L5178Y lymphoblasts treated with the adenosine deaminase inhibitor, 2'-deoxycoformycin, and deoxyadenosine. A synergistic antitumor effect was observed in resting cells between irradiation and 2'-deoxycoformycin/deoxyadenosine, with the dose required to reduce the surviving cell fraction to 0.1 being 25% lower than predicted for an additive effect. Synergy was enhanced with increasing deoxyadenosine concentration or with increasing radiation dose. When cells were treated with 2'-deoxycoformycin/deoxyadenosine for 1 h prior to irradiation, synergy was increased by prolonging postirradiation drug treatment. With 4-h postirradiation exposure to drug, varying the preirradiation incubation time did not affect synergy. In contrast, only a small enhancement of antitumor activity was observed in irradiated proliferating cells treated with 2'-deoxycoformycin/deoxyadenosine. Incubation of resting cells with 2'-deoxycoformycin/deoxyadenosine resulted in inhibition of the rate and extent of repair of radiation-induced DNA single strand breaks and an increase in dATP, but had no effect on NAD or ATP. With removal of drug, the dATP level fell rapidly and DNA repair resumed. Repair of DNA single strand breaks was more rapid in proliferating cells than in resting cells and was minimally affected by 2'-deoxycoformycin/deoxyadenosine, although the accumulation of dATP in these cells was 2-fold greater than in resting cells. The repair of DNA single strand breaks in chronic lymphocytic leukemia cells was as rapid as for proliferating L5178Y cells, but repair was significantly inhibited by 2'-deoxycoformycin/deoxyadenosine. These results suggest that 2'-deoxycoformycin/deoxyadenosine can function as a radiosensitizer, and this effect is associated with the cellular accumulation of dATP and inhibition of repair of DNA single strand breaks.

Adenosine Deaminase Inhibitors↗
PubMed1988

Characterization of L5178Y murine lymphoblasts resistant to quinone antitumor agents.

The exact contribution of the quinone group to the activity of quinone antitumor agents remains uncertain. Two L5178Y murine lymphoblastic cell lines resistant to the model quinone antitumor agent, hydrolyzed benzoquinone mustard, and one partial-revertant cell line were isolated and characterized. The antitumor activity of hydrolyzed benzoquinone mustard has been shown previously to be due to its ability to induce free radical mediated DNA strand breaks. Resistant cells were obtained by growing a cloned L5178Y parental cell line in media containing increasing concentrations of hydrolyzed benzoquinone mustard. L5178Y/HBM2 cells were selected from L5178Y cells growing in media containing 0.2 mM drug, while L5178Y/HBM10 cells were selected from cells growing in media containing 1.0 mM drug. The L5178Y/HBMR cells were obtained by growing L5178Y/HBM10 cells in media without hydrolyzed benzoquinone mustard. The resistant cell lines, L5178Y/HBM2 and L5178Y/HBM10, were 2.5- and 6-fold less sensitive, respectively, to hydrolyzed benzoquinone mustard compared to parental cells, and this was accompanied by a decrease in the formation of DNA single and double strand breaks by this drug. The partial-revertant cell line, L5178Y/HBMR was 2.9-fold less sensitive to hydrolyzed benzoquinone mustard compared to parental cells. Drug uptake appeared to be lower in the resistant cells compared to parental cells. The resistant cells had a slightly elevated level of superoxide dismutase activity compared to parental cells, but there was no increase in the mRNA for superoxide dismutase nor any amplification of the gene for this enzyme. Intracellular catalase activities of the L5178Y/HBM2 and L5178Y/HBM10 cells were elevated by 1.25- and 2.6-fold, respectively, and the increased enzyme activity in the L5178Y/HBM10 cells appeared to result from a 3.6-fold increase in mRNA for this enzyme. Glutathione peroxidase activity was slightly elevated in L5178Y/HBM2 cells, but was unchanged in the other resistant cells. The L5178Y/HBM2 and L5178Y/HBM10 cells showed increased concentrations of glutathione and elevated levels of glutathione transferase activity. The resistant cell lines also had DT-diaphorase activity that was 3- and 24-fold higher in L5178Y/HBM2 and L5178Y/HBM10 cells, respectively, compared to sensitive cells. However, cytochrome P-450 reductase activity and the ratio of reduced to oxidized pyridine nucleotides was unchanged in the resistant cell lines. The partial-revertant cell line, L5178Y/HBMR, showed approximately the same level of resistance to hydrolyzed benzoquinone mustard as the L5178Y/HBM2 cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Effects of 3'-(3-cyano-4-morpholinyl)-3'-deaminoadriamycin and structural analogues on DNA in HT-29 human colon carcinoma cells.

The potent Adriamycin (ADR) analogue, 3'-(3-cyano-4-morpholinyl)-3'-deaminoadriamycin (CMA), produces DNA-DNA cross-links in human and murine tumor cells. The cellular pharmacology of CMA, its derivative, 5-imino-3'-(3-cyano-4-morpholinyl)-3'-deaminoadriamycin (ICMA), 3'-(4-morpholinyl)-3'-deaminoadriamycin (MA), and ADR was evaluated in HT-29 human colon carcinoma cells to determine the structural requirements for the cross-linking activity of CMA, and the role of this activity in the antitumor effect of this agent. CMA was 50-fold more cytocidal than ICMA to HT-29 cells, 300-fold more toxic than MA, and 150-fold more potent than ADR. Both CMA and ICMA produced DNA-DNA cross-links in HT-29 cells but, consistent with its reduced cytotoxicity, the imino derivative was 30-fold less active than CMA. No DNA-DNA cross-links were observed with MA or ADR. CMA also showed cross-linking activity in isolated HT-29 nuclei, indicating that cytoplasmic activation was not required for this effect. Both CMA and ICMA produced cross-links in isolated lambda-phage DNA with CMA being 40-fold more active than the imino derivative, and this activity was unchanged in the presence or absence of a reducing agent. While MA and ADR produced DNA strand breaks in HT-29 cells, this damage was not observed with CMA and ICMA. This study indicates that the potent antitumor activity of CMA may be related to its ability to induce DNA cross-links, which can occur without the need for metabolic activation. The cyanide group appears to be essential for cross-linking and the quinone group may also be involved, but by a mechanism unrelated to its reduction.

Antineoplastic Agents↗
PubMed1987

Cellular pharmacology of 3'-(3-cyano-4-morpholinyl)-3'-deaminoadriamycin and structural analogues in human colon carcinoma HT-29 cells in vitro.

The new Adriamycin (ADR) analogue, 3'-(3-cyano-4-morpholinyl)-3'-deaminoadriamycin (CMA), is the most potent anthracycline yet developed. The cellular pharmacology of CMA and 3'-(4-morpholinyl)-3'-deaminoadriamycin (MA), and their 5-imino derivatives, ICMA and IMA, were compared with ADR in a human colon carcinoma (HT-29) cell line in vitro. In a soft agar clonogenic assay, the order of antitumor activity was CMA greater than ICMA greater than ADR greater than MA greater than IMA, for both 2- and 24-h drug exposure periods, indicating a requirement for the cyanide group and an intact quinone ring for the potent antitumor effect of CMA. The cellular uptake of CMA was 2-fold less than that of MA, although, consistent with its greater nuclear binding, the degree of efflux of CMA was less than that of MA. The order of cytotoxicity of the analogues correlated approximately with their effects on cellular DNA synthesis, indicating that this feature may contribute to the antitumor effect. Using isolated nuclei, the order of inhibition of DNA transcription by the analogues was CMA greater than MA greater than ADR, which was similar to their nuclear affinities, suggesting that their effects on cellular nucleic acid synthesis were due to a direct interaction of drug with DNA. However, CMA did not appear to differ from the other drugs in its base specificity as all the analogues preferentially inhibited Escherichia coli RNA polymerase activity directed by poly(dAdT).poly(dAdT) compared to poly(dGdC).poly(dGdC).

Adenocarcinoma↗
PubMed1987

Induction of DNA strand breaks in chronic lymphocytic leukemia following treatment with 2'-deoxycoformycin in vivo and in vitro.

Four patients with refractory chronic lymphocytic leukemia were treated with the adenosine deaminase inhibitor, 2'-deoxycoformycin, and initially received 4 mg/m2 i.v. weekly. Clinical responses to therapy varied: Patient A had a minimal response; whereas Patient D showed an 85% decrease in lymphocyte count at 2 wk; and Patients B and C had intermediate responses. The pretreatment mononuclear cell adenosine deaminase activities, which ranged from 1.6 to 44.6 nmol adenosine/h/10(6) cells, decreased to approximately 1 nmol adenosine /h/10(6) cells 24 h following 2'-deoxycoformycin, and increased to 15 to 50% of the pretreatment activity prior to the second drug treatment. The clinical response to 2'-deoxycoformycin was unrelated to the pre- or posttreatment adenosine deaminase activities or to the rate of return of enzyme activities following treatment. The plasma deoxyadenosine levels and the leukemic cell dATP concentrations rose slightly with therapy, but there was no correlation between the magnitude of increase and clinical response. No significant levels of DNA strand breaks were observed in the leukemic cells following treatment, although the NAD levels decreased slightly in two patients. When peripheral mononuclear cells from the patients and two controls were incubated in vitro for 24 h with 2'-deoxycoformycin and increasing concentrations of deoxyadenosine, a concentration-dependent increase in dATP and decrease in NAD were observed in both the patients and normals. The normal cells, and cells from two patients, developed a significant number of DNA strand breaks. However, there was no relationship between the formation of DNA breaks and the degree of accumulation of dATP or depletion of NAD, or between any of these changes and subsequent clinical responses to 2'-deoxycoformycin. Based on this study, it appears that the antitumor activity of 2'-deoxycoformycin in chronic lymphocytic leukemia is unrelated to the induction of DNA strand breaks or to changes in the levels of dATP or NAD in the leukemic cells.

Adenosine Deaminase Inhibitors↗
PubMed1986

The retrocuspid papillae in Israeli Jews.

The prevalence of an anatomic variation, called retrocuspid papilla, was determined in Israeli Jews. The distribution of the retrocuspid papillae, according to two age groups, and symmetry within the dental arch and in relation to ethnic origin were examined. Results showed that retrocuspid papillae were observed in 38.5% of the young group and in 11.3% of the adult group. Greater occurrence of bilateral than unilateral retrocuspid papillae was observed in each age group and in both sexes. No significant ethnic trend was found when the prevalence of retrocuspid papillae was examined in relation to the ethnic origin of the study sample.

Adolescent↗
PubMed1986

Effects of 3'-(4-morpholinyl)-3'-deaminodaunorubicin,3'- (4-methoxy-1-piperidinyl)-3'-deaminodaunorubicin and daunorubicin on nuclear and polysomal RNA synthesis in human colon carcinoma cells in vitro.

The sugar amine modified anthracyclines, 3'-(4-morpholinyl)-3'-deaminodaunorubicin (MD) and 3'-(4-methoxy-1-piperidinyl)-3'-deaminodaunorubicin (MEO), are 10-fold more potent than daunorubicin (DAU) as inhibitors of RNA synthesis in human colon carcinoma (HT-29) cells in vitro, although they are 10-fold less cytocidal. In this study, HT-29 cells were exposed for 2 h to 5 X 10(-8) M MD or MEO, or 5 X 10(-7) M DAU; under these conditions total RNA synthesis is decreased by each drug by 50%, whereas cell viability is reduced more than 99% by DAU, but less than 10% by MD and MEO. Following the 2-h exposure, the cellular content of DAU was 2-4-fold greater than that of MEO and MD, respectively. All three drugs had a similar inhibitory effect on the different nuclear RNA fractions and preferentially reduced nucleolar RNA synthesis (44-49% inhibition) compared to heterogeneous RNA synthesis (5% inhibition). Polysomal RNA synthesis was inhibited to a greater degree than nuclear RNA synthesis by all the anthracyclines, and non-poly RNA synthesis was decreased by 50-60% and poly(A) RNA synthesis by 30%. When treated cells were incubated in drug-free medium for 2 h, RNA synthesis returned to 80% of the pretreatment level in MD and DAU treated cells, but by less than 10% in cells treated with MEO, and this difference was due to the more rapid cellular efflux of MD and DAU versus MEO. Thus, MD and MEO are inherently more potent inhibitors than DAU of RNA synthesis in HT-29 cells, but their reduced cytotoxicity cannot be attributed to differing effects on nucleolar or heterogeneous RNA synthesis, the nucleocytoplasmic transport of RNA, or the rate of return of RNA synthesis following drug treatment.

Antineoplastic Agents↗
PubMed1986

The contribution of alkylation to the activity of quinone antitumor agents.

Studies have shown that the quinone group can produce tumor cell kill by a mechanism involving active oxygen species. This cytotoxic activity can be correlated with the induction of DNA double strand breaks and is enhanced by the ability of the quinone compound to bind to DNA by alkylation. The cytotoxic activity and the production of DNA damage by model quinone antitumor agents were compared in L5178Y cells, sensitive and resistant to alkylating agents, to assess the contribution of alkylation to the activity of these agents. The resistant L5178Y/HN2 cells were found to be two fold and six fold more resistant to the alkylating quinones, benzoquinone mustard and benzoquinone dimustard, respectively, than parent L5178Y cells. In contrast, the L5178Y/HN2 cells showed no resistance to the nonalkylating quinones, hydrolyzed benzoquinone mustard and bis(dimethylamino)benzoquinone. The alkylating quinones produced approximately two fold less cross-linking in L5178Y/HN2 cells compared with L5178Y sensitive cells. DNA double strand break formation by hydrolyzed benzoquinone mustard and bis(dimethylamino)benzoquinone was not significantly different in sensitive and resistant cells. However, the induction of double strand breaks by the alkylating quinones benzoquinone mustard and benzoquinone dimustard was reduced by 5-fold and 15-fold, respectively, in L5178Y/HN2 cells. These results show that the alkylating activity of the alkylating quinones cannot directly explain all of the enhanced cytotoxic activity of these agents. Furthermore, they provide strong evidence that the enhanced formation of DNA double strand breaks by alkylating quinone agents is directly related to the ability of these agents to bind to DNA. This increased formation of strand breaks may account for the enhanced cytotoxic activity of the alkylating quinones.

Alkylating Agents↗
PubMed1986

Biochemical changes induced in hairy-cell leukemia following treatment with the adenosine deaminase inhibitor 2'-deoxycoformycin.

The adenosine deaminase inhibitor 2'-deoxycoformycin and interferon are highly effective in the treatment of hairy-cell leukemia. In this study, a patient with type 2 hairy-cell leukemia was treated with one cycle of 2'-deoxycoformycin (4 mg/m2, i.v. weekly for 3 weeks), which was repeated at 9 wk. No toxicity was observed, and the hairy cell count fell from 72,000/mm3 to 5,000/mm3 in 3 mo, with a concomitant 50% decrease in the spleen size. The erythrocyte deoxyadenosine triphosphate content increased to 13.6 pmol/10(6) cells following the initial three weekly treatments, but there was no decrease in the adenosine triphosphate pool size and no evidence of hemolysis. The hairy cell adenosine deaminase activity was inhibited by greater than 95% 24 h following the first 2'-deoxycoformycin injection and returned to the pretreatment value at Day 8, although there was a linear decline in peripheral hairy cell count (50%) during this period. No ultrastructural changes were observed in the hairy cells following 2'-deoxycoformycin to suggest lymphocytotoxicity or cellular differentiation. The antitumor activity of 2'-deoxycoformycin could not be attributed to alterations in the hairy cell deoxyadenosine triphosphate/adenosine triphosphate levels or to the induction of DNA strand breaks. Additionally, the plasma levels of interferon did not change during therapy, making it unlikely that 2'-deoxycoformycin exerts its activity by inducing endogenous interferon synthesis.

Adenosine↗
PubMed1985

DNA crosslinking by 3'-(3-cyano-4-morpholinyl)-3'-deaminoadriamycin in HT-29 human colon carcinoma cells in vitro.

The Adriamycin analog, 3'-(3-cyano-4-morpholinyl)-3'-deaminoadriamycin, is 100- to 1000-fold more active than Adriamycin as an antitumor agent in vivo and in vitro. The interaction of 3'-(3-cyano-4-morpholinyl)-3'deaminoadriamycin and Adriamycin with DNA has been studied in HT-29 human colon carcinoma cells in vitro. The Adriamycin analog produced significant DNA-DNA crosslinking at a drug concentration range that resulted in from 1 to 4 logs of cell kill, but did not produce any DNA-protein crosslinks. Equitoxic concentrations of Adriamycin produced no significant levels of DNA-DNA crosslinks. The formation of DNA-DNA crosslinks by the Adriamycin derivative is an additional mechanism of action that may account for the high potency of this agent.

Cell Line↗
PubMed1985

Studies on the mechanism of action of quinone antitumor agents.

The presence of a quinone group in the structure of a compound has been shown to produce cell kill and DNA strand breaks by a mechanism involving free radicals and active oxygen species. The ability of the compound to bind to DNA appeared to increase the DNA damage induced and the cytotoxic activity. A new series of model compounds has been used to investigate further the role of the quinone group in the mechanism of action of quinone antitumor agents. Bis(dimethylamino)benzoquinone, which contains a quinone group, produced significant cell kill of L5178Y lymphoblasts and induced concentration-dependent single-strand and double-strand breaks in the DNA of these cells. Benzoquinone dimustard, which possesses a quinone moiety and active alkylating groups, was approximately 2500 times more cycotoxic to L5178Y cells than was bis(dimethylamino)benzoquinone and was approximately 200-fold more active in inducing DNA double-strand breaks than was the quinone agent. Benzoquinone dimustard induced no apparent DNA single-strand breaks, but produced significant DNA cross-linking, a process which interferes with the assay for single-strand breaks. The cell kill produced by both quinone agents was inhibited by catalase, but not by superoxide dismutase. The cytotoxic activity of bis(dimethylamino)benzoquinone and two other quinone model compounds, hydrolyzed benzoquinone mustard and benzoquinone mustard, appeared to correlate with the induction of DNA strand breaks, while there appeared to be no correlation between cell kill and DNA double-strand breaks induced by benzoquinone dimustard. However, the cytotoxicity of benzoquinone dimustard appeared to be related to the cross-linking activity of this agent. These studies have provided additional evidence that the presence of a quinone group in the structure of a compound can result in significant cell kill by a mechanism that appears to involve active oxygen species. Quinone containing agents can induce DNA strand breaks, and this effect is enhanced when the agent is able to bind to DNA. The induction of DNA strand breaks appeared to correlate with cytotoxic activity for bis(dimethylamino)benzoquinone, hydrolyzed benzoquinone mustard and benzoquinone mustard, but not for benzoquinone dimustard, suggesting that the contribution of quinone-induced strand breaks to the overall cytotoxicity of an agent may vary considerably.

Animals↗
PubMed1984

Quinone-induced DNA damage and its relationship to antitumor activity in L5178Y lymphoblasts.

The presence of a quinone group in the structure of a series of model compounds was shown to produce cell kill by a mechanism involving free radicals and active oxygen species. Furthermore, the ability of the compound to bind to DNA appeared to enhance its cytocidal activity. The same model compounds were used to investigate the effect of the quinone group on cellular DNA. DNA single-strand breaks, DNA double-strand breaks, and DNA-DNA cross-linking induced by the model compounds were measured by elution assays. Hydrolyzed benzoquinone mustard, which contains a quinone group, induced dose-dependent single-strand and double-strand breaks but no DNA cross-linking. Benzoquinone mustard, which possesses both a quinone moiety and an active alkylating group, produced dose-dependent DNA double-strand breaks but no apparent single-strand breaks. However, this compound produced significant levels of DNA cross-linking, a process which interferes with the assay for single-strand breaks. The relative activity of benzoquinone mustard in inducing DNA double-strand breaks was approximately 15,000-fold greater than that of hydrolyzed benzoquinone mustard. Aniline mustard, which has the same alkylating group as does benzoquinone mustard but no quinone function, produced lower levels of DNA-DNA cross-links and no DNA strand breaks. The induction of both DNA single-strand and double-strand breaks by hydrolyzed benzoquinone mustard was significantly inhibited by the cell-protective enzymes superoxide dismutase and catalase. The cytotoxic activity of hydrolyzed benzoquinone mustard appeared to correlate with the induction of DNA single- and double-strand breaks. These studies provided evidence that the presence of a quinone group in the chemical structure of a compound results in the production of DNA strand breaks. DNA damage was inhibited by superoxide dismutase and catalase, suggesting the involvement of free radicals and active oxygen species. The induction of DNA damage appeared to be enhanced by the ability of the compound to bind to DNA. The induction of strand breaks may correlate with the cytotoxic activity of the quinone agents.

Aniline Mustard↗