3-Aminobenzamide

log Kow = -0.33

-0.33

Warning

H302 (87%): Harmful if swallowed [Warning Acute toxicity, oral]

P261, P264, P264+P265, P270, P271, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 46 reports by companies from 6 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Chronic irradiation (three times a week) with ultraviolet B light of the skin of hairless mouse Uscd (Hr) strains resulted in the induction of skin tumors after 25 to 41 weeks. Topical applications of 3-aminobenzamide (3AB; 0.1 or 1 M) after each irradiation significantly shortened the earliest time of onset of tumors to 13 to 25 weeks and increased the number of animals that developed tumors over 41 weeks from 67% without 3AB to 73% and 81% with 0.1 and 1 M 3AB, respectively. ...

The poly(ADP-ribosyl)transferase inhibitor, 3-aminobenzamide (3-ABA), reduced morphological evidence of 1,2-dibromo-3-chloropropane (DBCP)-induced DNA damage determined by alkaline elution. The DBCP plasma, kidney, and testis tissue doses determined between 1 and 8 hr after a single intraperitoneal injection were somewhat higher with than without 3-ABA pretreatment. Furthermore, the amount of DBCP metabolites covalently bound to macromolecules was reduced to about 20-30 percent of control, indicating that 3-ABA may have an effect on the formation/detoxication of reactive DBCP metabolites. ...

... 3-aminobenzamide (3AB) combined with X-rays was used to evaluate the micronucleus dose-response relationship in /in vitro-irradiated lymphocytes/ blood from 14 individuals. While it is known that 3AB inhibits poly(ADP-ribose) polymerase activity in vitro, ... it also increases the X-ray-induced micronucleus yields. The resulting dose-response relationship varies from subject to subject. ...

Gene expression of human immunodeficiency virus type 1 (HIV-1) is induced not only by trans activation mediated through a gene product (tat) encoded by the virus but also by treatment of virus-carrying cells with DNA-damaging agents such as UV light. Employing an artificially constructed DNA in which the chloramphenicol acetyltransferase gene was placed under the control of the HIV-1 long terminal repeat, ... the induction process in HeLa cells /was analyzed/ and ... inhibitors of poly(ADP-ribose) polymerase /including 3-aminobenzamide/ suppressed UV-induced HIV-1 gene expression but not tat-mediated expression. ... Suppression occurs at the posttranscriptional level. These results indicate that HIV-1 gene expression is activated by at least two different mechanisms, one of which involves poly-ADP ribosylation. ...

Synergistically enhanced sister chromatid exchange (SCE) frequency by cyclophosphamide (CP) was observed when L1210 lymphoid tumor cells were exposed in vivo to a non-toxic concentration of 3-aminobenzamide (3-AB). Additive effects in SCE induction in vivo were observed when either Ehrlich ascites tumor (EAT) cells or P388 lymphocytic leukemia cells treated with CP were exposed to 3-AB in vivo. 3-AB enhanced the survival time of L1210 tumor bearing BDF1 mice treated with CP. However, the combined CP plus 3-AB treatment did not increase the survival of either EAT BALB/c- or P388 BDF1-tumor bearing mice compared with the effect on survival by CP alone. Therefore the in vivo differential antitumor effect, by CP in conjunction with 3-AB, appears to correlate well with the in vivo differential effect on cytogenetic damage caused by the combined CP plus 3-AB treatment. In the Salmonella typhimurium/mammalian microsome test CP appears to have a dose dependent ability to induce base-pair substitutions in strains TA 100 and TA 1535 and frameshift mutations in strains TA 98 and TA 1537. Both types of mutation were synergistically increased in the presence of 3-AB.

/ALTERNATIVE and IN VITRO TESTS/ A /human fibroblast/ cell line deficient in DNA ligase I and sensitive to poly(ADP-ribose) inhibitors, 46BR, was used to examine the relationship between DNA ligation and a large stimulation of repair replication that is seen in cells grown in a poly(ADP-ribose) polymerase inhibitor, 3-aminobenzamide (3AB), after exposure to alkylating agents. Repair replication was stimulated at least 10-fold by 3AB in both normal and ligase-deficient cells. Despite increased 3AB toxicity, repair replication in ligase I-deficient cells was unchanged from that in normal cells. This evidence is consistent with previous observations that the enhancement of repair replication by 3AB is not a direct function of DNA break frequencies. The stimulation may instead result from alkylation damage to other cellular organelles that release nucleases that cause additional damage to DNA, which cells attempt to repair.

/GENOTOXICITY/ ... The effect of 3-aminobenzamide (3AB) in gamma-irradiation induced damage and the subsequent repair of DNA along with the corresponding changes in poly (ADP-ribose) polymerase activity in lymphocytes of patients with cancer of breast and uterine cervix /was studied/. The presence or absence of 3AB prior to gamma-irradiation did not influence the extent of DNA damage. On the other hand, single strand break rejoining in breast cancer cases was found to be slower as compared to that of cervical cancer cases and normal individuals. The relative ADP-ribosylation in the presence of 3AB was much lower in the breast cancer cases as compared to normal but there was no significant change in the cervical cancer cases. Overall the maximum relative ADP-ribosylation was slower in the presence of 3AB. This suggests that the lower activity of poly (ADP-ribose) polymerase in breast cancer cases might delay the first phase of single strand breaks (SSBs) rejoining.

/GENOTOXICITY/ Effects of 5-hydroxymethyl-2'-deoxyuridine (HmdUrd, a thymidine analog) and 3-aminobenzamide (3AB) on chromosome aberrations in cultured human lymphocytes were studied. The results show that HmdUrd is an effective clastogen in human peripheral lymphocytes. When cells were treated with HmdUrd and 3AB, a synergistic effect on chromatid gaps, breaks and exchanges was found. These findings support the hypotheses that 5-hydroxymethyluracil (HmUra) residues in DNA are formed and then removed by the action of 5-HmUra-DNA glycosylase ... and that 3AB interferes with the completion of DNA repair following HmUra excision.

/LABORATORY ANIMALS: Acute Exposure/ There have been no previous studies of the effects of poly(ADP-ribose) polymerase (PARP) inhibitors on N-methyl-N-nitrosourea (MNU)-induced cataractogenesis in rats. A single intraperitoneal injection of 70 mg/kg MNU was administered to 15-day-old male and female Sprague-Dawley rats. In Experiment 1, rats were then subcutaneously injected with 1000 mg/kg nicotinamide either once or 3 times at 1-week intervals. In Experiment 2, rats were subcutaneously injected once with 50 mg/kg 3-aminobenzamide. For comparison, the following age-matched controls were included: MNU-untreated nicotinamide-injected rats, MNU-untreated 3-aminobenzamide-injected rats, and MNU-untreated PARP-inhibitor-untreated rats. Rats were examined for lens opacity. At 28 days after MNU injection, 10 to 20 rats per group were sacrificed. In Experiment 1, at 3 days after MNU injection, 10 rats per group were sacrificed for apoptosis and cell proliferation detection. MNU caused lens epithelial cell apoptosis in the germinative zone, as indicated by TUNEL staining. However, regardless of MNU treatment lens epithelial cell proliferation was consistently seen in the germinative zone and sporadically seen in the central zone. At 28 days after MNU, mature cataracts were observed. Nicotinamide significantly accelerated lens opacity and cataractogenesis, as indicated by a cataract index. 3-Aminobenzamide significantly accelerated the development of lens opacity and tended to accelerate cataractogenesis. The PARP inhibitors nicotinamide and 3-aminobenzamide accelerated MNU-induced cataractogenesis.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Effects of 3-aminobenzamide (ABA) on pancreatic carcinogenesis after initiation by N-nitrosobis(2-oxopropyl)amine (BOP) were investigated in Syrian hamsters. Animals were given BOP at a dose of 70 mg/kg body weight by sc injection and following a 2-week recovery period, were administered basal diet or basal diet containing 0.5, 0.75 and 1.5% ABA for 30 weeks. While the incidences of resultant pancreatic lesions, including hyperplasia, atypical hyperplasia and carcinoma, induced by BOP were not significantly influenced by ABA treatment, the mean numbers of those pancreatic lesions were significantly decreased in a dose-dependent way. The results therefore suggested the possible involvement of poly(ADP-ribosyl)ation in the post-initiation phase of pancreatic carcinogenesis in hamsters.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ The effects of inhibitors of poly(ADP-ribose)polymerase, 3-aminobenzamide (ABA), luminol and 3-methoxybenzamide (MBA) on the rat liver tumor promotion activity of phenobarbital (PB) were assessed. Fischer 344 male rats were initiated with N-nitrosodiethylamine (200 mg/kg) and placed on either basal diet, diet containing 0.05% PB, diet containing various doses of the inhibitors alone or diet containing 0.05% PB plus various doses of inhibitors for 10 weeks, and then killed. Quantitation of the development of glutathione S-transferase placental form-positive foci revealed that ABA at doses of 2 and 1.5, but not 1%, significantly inhibited the PB promotion activity. Luminol dose-dependently reduced PB promotion at doses of 3 and 6% but exerted no effects at the 1 and 2% levels. MBA also demonstrated a dose-dependent inhibitory influence at doses of 1 and 2%.

/ALTERNATIVE and IN VITRO TESTS/ Damage of 3T3 fibroblasts as induced by short-term co-cultivation with O2(-)-producing granulocytes, stimulated by 12-O-tetradecanoyl-phorbol-13-acetate (TPA), was compared with that induced by treatment with enzymically generated O2- and with the alkylating agent dimethyl sulfate. ... 3-Aminobenzamide, the most widely used inhibitor of ADP-ribosylation, partially protected target cells from the cytotoxic effects of TPA-stimulated granulocytes, while it enhanced alkylation-induced and O2(-)-induced cytotoxicity. Protection by 3-aminobenzamide in the granulocyte system was apparently not mediated by an inhibition of nuclear poly(ADP-ribosyl)ation. ... The unique effect of 3-aminobenzamide in this system appeared to relate to TPA-induced adhesion of the neutrophils to surfaces. In the presence of 1 mM 3-aminobenzamide, but not of benzamide, the adhesion of stimulated granulocytes to 3T3 monolayer cultures was markedly reduced or even abolished. This effect was also seen in granulocyte preparations depleted of monocytes. Since 3-aminobenzamide at the doses applied does not inhibit TPA-induced superoxide production in isolated granulocytes, its specific anticytotoxic effect appears to result from a dilution of granulocyte-derived damaging agents into the medium. ... Prevention of granulocyte adhesion is likely to reduce tissue damage and carcinogenesis in areas of chronic inflammation.

/GENOTOXICITY/ In SVM cells, an SV40-transformed line of Indian muntjac fibroblasts, levels of sister-chromatid exchanges are known to be abnormally high after UV-irradiation or alkylation. The SVM line is also known to have a defect in the processing of DNA-strand breaks. Sister-chromatid exchange in other cells is known to be stimulated by the poly(ADP-ribose) transferase inhibitor, 3-aminobenzamide, which also retards DNA-break sealing. Sister-chromatid exchanges in SVM cells are found to be hypersensitive to 3-aminobenzamide, or to nicotinamide deprivation which similarly inhibits poly(ADP-ribosyl)ation; DNA-strand breaks are likewise induced by 3-aminobenzamide. Bromodeoxyuridine, needed to detect sister-chromatid exchanges, is more toxic to SVM cells and itself induces sister-chromatid exchanges to a greater extent than it does in normal muntjac cells. ... The mechanism by which BrdU exerts its effects can largely be explained in terms of familiar effects on deoxyribonucleotide pools and DNA integrity. 3-Aminobenzamide, however, induces sister-chromatid exchanges in SVM cells by another mechanism.

Poly(ADP-ribosyl)transferase inhibitor

A 3 hr exposure to 1 mM H2O2 followed by 6 hr post-challenge growth in peroxide-free medium induces necrosis in U937 cells. Addition of the poly(ADP-ribose)polymerase inhibitor 3-aminobenzamide during recovery prevents necrosis and triggers apoptosis, as shown by the appearance of apoptotic bodies, extensive blebbing and formation of multimeric DNA fragments as well as 50 kb double stranded DNA fragments. Thus, the same initial damage can be a triggering event for both apoptotic and necrotic cell death. Furthermore, necrosis does not appear to be a passive response to overwhelming damage.

Treatment with 3-aminobenzamide, known as an inhibitor of poly(ADP-ribose)polymerease, decreased the toxicity and covalent binding of the herbicide dichlobenil (2,6-dichlorobenzonitrile; 12 mg/kg; i.p.) in the mouse olfactory mucosa. In vitro studies showed that 3-aminobenzamide markedly reduced the NADPH-dependent covalent binding of [14C]dichlobenil and the hydroxylation of p-nitrophenol which have previously been suggested to be mediated by a common form of cytochrome P450 (P450) in rat olfactory microsomes ... . Furthermore, 3-aminobenzamide markedly reduced the P450-dependent metabolic activation of [3H]NNK (4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone) in rat olfactory microsomes and slightly decreased the P450 2B1-dependent pentoxyresorufindealkylase activity in liver microsomes of phenobarbital-treated rats. The present results suggest that 3-aminobenzamide is also an inhibitor of P450 and that the lack of toxicity of dichlobenil in the olfactory mucosa of 3-aminobenzamide-treated mice is related to a decreased metabolic activation of dichlobenil at this site... .

... Cll lines deficient in poly(ADP-ribose) synthesis due to deficiency in the enzyme poly(ADP-ribose) polymerase (PADPRP) or depletion of its substrate NAD+ overexpress GRP78. Furthermore, this overexpression of GRP78 is associated with the acquisition of resistance to topoisomerase II-directed drugs such as etoposide (VP-16) ... Thus, /the/ studies suggest that interference with NAD+-PADPRP metabolism could provide an important approach to (a) define pathways of GRP78 induction, (b) study the effect of GRP78 on other cellular processes, (c) elucidate the mechanism of GRP78-dependent resistance to topoisomerase II targeted drugs, and (d) modulate responses to chemotherapy in normal and tumor tissues. However, in the in vivo situation, it is impractical to interfere with NAD+-PADPRP metabolism by mutational inactivation of PADPRP or by depletion of its substrate NAD+. Therefore, ... several inhibitors of NAD+-PADPRP metabolism including 3-aminobenzamide, PD128763, and 6-aminonicotinamide /were examined/ for their ability to reproduce the results obtained with cell lines deficient in NAD+-PADPRP metabolism relative to the induction of GRP78 and subsequent development of resistance to VP-16. ... 6-aminoicotinamide treatment is highly effective in the induction of GRP78 and subsequent development of resistance to VP-16, whereas treatment with 3-aminobenzamide or PD128763 does not induce GRP78 and thus does not result in VP-16 resistance.

For more Mechanism of Action (Complete) data for 3-AMINOBENZAMIDE (7 total), please visit the HSDB record page.

3-Aminobenzamide (3-ABA) is a potent radiosensitizer that inhibits the repair of DNA strand breaks. The aim of this study was to monitor the biodistribution and pharmacokinetics of a fluorinated 3-ABA derivative in tumor-bearing rats by magnetic resonance imaging (MRI). To this end, 3-ABA was labeled with fluorine-19 by trifluoroethylation [3-amino-N-2,2,2-trifluoroethylbenzamide (3-ABA-TFE)], which only slightly increased the cytotoxicity of the compound as demonstrated by colony-forming assays. After intraperitoneal injection of 400 mg/kg BW 3-ABA-TFE to nine Copenhagen rats with Dunning prostate adenocarcinoma, (19)F MR images were acquired at a whole-body MR system with a spatial sampling of 10 x 10 x 15 mm(3). While 3-ABA-TFE was observed in all major organs and the muscular system, only a small and heterogeneous signal could be detected in the adenocarcinoma. Serial MR measurements yielded maximum tissue signals about 2 days after 3-ABA-TFE administration. At this time point, the mean muscle-to-liver and tumor-to-liver signal ratio was 0.31+/-0.07 and 0.11+/-0.04, respectively. Application of the (19)F MRI strategy makes it possible to measure the biodistribution and pharmacokinetics of 3-ABA-TFE in individual animals in a longitudinal manner. The results obtained for the prostate adenocarcinoma indicate that delivery of 3-ABA-TFE to solid tumors may be seriously hampered by tumor-specific factors and that the intratumoral uptake of the substance may be lower than in normal tissues. Therefore, the development of effective carrier systems is mandatory to improve tumor-selective delivery.

Chemicals and drugs that inhibit the action of POLY(ADP-RIBOSE)POLYMERASES.

Drugs used to potentiate the effectiveness of radiation therapy in destroying unwanted cells.

Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids.