Diane E. Heck
New York Medical College
ProdrugCytotoxicityDNA damageMolecular biologyChemistryPhototoxicitySuperoxide dismutaseInflammationKeratinocyteNitric oxide synthaseDermisNitrogen mustardMethoxsalenAnti-inflammatoryGrowth inhibitionWound healingSulfur mustardPsoralenPhotosensitizerCell cycleUltraviolet lightDegranulationDNABiochemistryCell biologyPharmacology
15Publications
4H-index
47Citations
Publications 15
Newest
#1Vladimir Mishin (RU: Rutgers University)H-Index: 18
#2Diane E. Heck (NYMC: New York Medical College)H-Index: 4
Last. Jeffrey D. Laskin (RU: Rutgers University)H-Index: 69
view all 4 authors...
A sensitive fluorescence assay based on Amplex Red (AR) oxidation by horseradish peroxidase (AR/HRP) is described which continuously monitor rates of H2O2 production by microsomal enzymes in the pr...
2 CitationsSource
#1Jeffrey D. Laskin (RU: Rutgers University)H-Index: 69
#2Gabriella Wahler (RU: Rutgers University)H-Index: 1
Last. Laurie B. Joseph (RU: Rutgers University)H-Index: 12
view all 7 authors...
Abstract Sulfur mustard (SM), a dermal vesicant that has been used in chemical warfare, causes inflammation, edema and epidermal erosions depending on the dose and time following exposure. Herein, a minipig model was used to characterize wound healing following dermal exposure to SM. Saturated SM vapor caps were placed on the dorsal flanks of 3-month-old male Gottingen minipigs for 30 min. After 48 h the control and SM wounded sites were debrided daily for 7 days with wet to wet saline gauze soa...
1 CitationsSource
#1Christophe Guillon (Lehigh University)H-Index: 8
#2Anna M. Vetrano (RU: Rutgers University)H-Index: 15
Last. Jeffrey D. Laskin (RU: Rutgers University)H-Index: 69
view all 13 authors...
Abstract A set of 4-(R2-imino)-3-mercapto-5-(R1)-4H-1,2,4-triazoles derivatives were synthesized, characterized and evaluated for their ability to inhibit nitric oxide (NO) production in PAM212 mouse keratinocytes, which led to the discovery and the subsequent evaluation of their growth inhibitory cytotoxic potency toward that same mouse cell line together with a number of human cells lines (PC3, HT-29 and HeLa). Some limited SAR could be established for both NO production inhibition potency and...
2 CitationsSource
#1Yi-Hua Jan (RU: Rutgers University)H-Index: 8
#2Diane E. Heck (NYMC: New York Medical College)H-Index: 4
Last. Jeffrey D. Laskin (RU: Rutgers University)H-Index: 69
view all 4 authors...
Abstract Mustard vesicants, including sulfur mustard (2,2′-dichlorodiethyl sulfide, SM) and nitrogen mustard (bis(2-chloroethyl)methylamine, HN2) are cytotoxic blistering agents synthesized for chemical warfare. Because they contain highly reactive electrophilic chloroethyl side chains, they readily react with cellular macromolecules like DNA forming monofunctional and bifunctional adducts. By targeting DNA, mustards can compromise genomic integrity, disrupt the cell cycle, and cause mutations a...
3 CitationsSource
#1Gabriella Wahler (RU: Rutgers University)H-Index: 1
#2Diane E. Heck (NYMC: New York Medical College)H-Index: 4
Last. Laurie B. Joseph (RU: Rutgers University)H-Index: 12
view all 6 authors...
Abstract Nitrogen mustard (NM) is a highly reactive bifunctional alkylating agent that induces inflammation, edema and blistering in skin. An important mechanism mediating the action of NM and related mustards is oxidative stress. In these studies a modified murine patch-test model was used to analyze DNA damage and the antioxidant/stress response following NM exposure in isolated epidermis. NM (20 μmol) was applied to glass microfiber filters affixed to a shaved dorsal region of skin of CD-1 mi...
1 CitationsSource
#1Christophe Guillon (Lehigh University)H-Index: 8
#2Yi Hua Jan (RU: Rutgers University)H-Index: 3
Last. Ned D. Heindel (Lehigh University)H-Index: 20
view all 12 authors...
Abstract Seventy-one 7-oxycoumarins, 66 synthesized and 5 commercially sourced, were tested for their ability to inhibit growth in murine PAM212 keratinocytes. Forty-nine compounds from the library demonstrated light-induced lethality. None was toxic in the absence of UVA light. Structure-activity correlations indicate that the ability of the compounds to inhibit cell growth was dependent not only on their physiochemical characteristics, but also on their ability to absorb UVA light. Relative li...
1 CitationsSource
#1Yi Hua Jan (RU: Rutgers University)H-Index: 3
#2Diane E. Heck (NYMC: New York Medical College)H-Index: 4
Last. Jeffrey D. Laskin (RU: Rutgers University)H-Index: 69
view all 4 authors...
Nitrogen mustard, mechlorethamine (bis(2-chloroethyl)methylamine; HN2), and sulfur mustard are potent vesicants that modify and disrupt cellular macromolecules including DNA leading to cytotoxicity and tissue injury. In many cell types, HN2 upregulates DNA damage signaling pathways including ataxia telangiectasia mutated (ATM), ataxia telangiectasia mutated- and Rad3-related (ATR) as well as DNA-dependent protein kinase (DNA-PK). In the present studies, we investigated crosstalk between the HN2-...
7 CitationsSource
#1Christophe Guillon (Lehigh University)H-Index: 8
#2Yi-Hua Jan (RU: Rutgers University)H-Index: 8
Last. Ned D. Heindel (Lehigh University)H-Index: 20
view all 7 authors...
Abstract Linear furocoumarins, also known as psoralens, are clinically useful photo-activated pharmaceuticals employed to address hyperproliferative skin diseases. Seven diverse cytotoxic pharmacophores have been synthetically attached to 8-methoxypsoralen via a 5-amino functionality. The resulting unique set of compounds was evaluated for dark and light toxicity against PAM212 keratinocytes in culture.
4 CitationsSource
#1John T. Szilagyi (RU: Rutgers University)H-Index: 4
#2Karma C. Fussell (RU: Rutgers University)H-Index: 3
Last. Jeffrey D. Laskin (RU: Rutgers University)H-Index: 69
view all 11 authors...
Abstract NADH cytochrome b5 reductase mediates electron transfer from NADH to cytochrome b5 utilizing flavin adenine dinucleotide as a redox cofactor. Reduced cytochrome b5 is an important cofactor in many metabolic reactions including cytochrome P450-mediated xenobiotic metabolism, steroid biosynthesis and fatty acid metabolism, hemoglobin reduction, and methionine and plasmalogen synthesis. Using recombinant human enzyme, we discovered that cytochrome b5 reductase mediates redox cycling of a v...
4 CitationsSource
#1Laurie B. Joseph (RU: Rutgers University)H-Index: 12
#2Gabriella M. Composto (RU: Rutgers University)H-Index: 5
Last. Diane E. Heck (NYMC: New York Medical College)H-Index: 4
view all 13 authors...
Abstract Sulfur mustard (SM, bis(2-chloroethyl sulfide) is a potent vesicating agent known to cause skin inflammation, necrosis and blistering. Evidence suggests that inflammatory cells and mediators that they generate are important in the pathogenic responses to SM. In the present studies we investigated the role of mast cells in SM-induced skin injury using a murine vapor cup exposure model. Mast cells, identified by toluidine blue staining, were localized in the dermis, adjacent to dermal app...
9 CitationsSource