Cytotoxicity of methyl methacrylate (MMA) and related compounds and their interaction with dipalmitoylphosphatidylcholine (DPPC) liposomes as a model for biomembranes.
OBJECTIVE
To clarify the potential mechanism of action of methyl methacrylate (MMA) and related compounds to membranes of living cells, compared with their interaction with dipalmitoylphosphatidylcholine (DPPC) liposomes as a model for biological membranes.


METHODS
For (meth)acrylates, MMA, ethyl acrylate(EA), n-butyl acrylate (BA) and n-butyl methacrylate (BMA) and for living cells, primary human gingival fibroblast (HGF), human submandibular gland adenocarcinoma cell line (HSG) and human erythrocytes were used. The physicochemical changes in DPPC liposomes induced by (meth)acrylates were studied using differential scanning calorimetry (DSC) and nuclear magnetic resonance spectroscopy (NMR).


RESULTS
Cytotoxicity decreased as follows: BA > BMA > EA > MMA. Changes in phase transition properties (temperature Tm, enthalpy delta H and Height/Half-Height Width (H/HHW) of DSC peak were decreased as follows: BA > EA > MMA. BMA enhanced H/HHW and increased Tm slightly. NMR-shielding effect decreased as follows: BMA > MMA > BA, EA.


CONCLUSIONS
BA and BMA exhibited large cytotoxicity and high DPPC-interaction due to their lipophilicity, compared to EA or MMA. MMA showed little cytotoxicity and small changes in DPPC liposomes, whereas BA showed large cytotoxicity and large changes in the liposomes characterized by the membrane disturbance. Haemolytic activity and cytotoxicity of acrylates were higher than those of methacrylates. The physico-chemical properties (Log P or Q sigma) of (meth)acrylates affect the lipid bilayer in biological membranes.
Fujisawa
S
S
Department of Oral Diagnosis, Meikai University, School of Dentistry, Sakado, Saitama-ken, 3500283, Japan.
Atsumi
T
T
Kadoma
Y
Y
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry*; D000179:Acrylates / Q000737:chemistry* / Q000633:toxicity; D000230:Adenocarcinoma / Q000473:pathology; D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005881:Gingiva / Q000166:cytology / Q000187:drug effects; D006461:Hemolysis; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry; D008081:Liposomes; D009682:Magnetic Resonance Spectroscopy; D008567:Membranes, Artificial; D008689:Methacrylates / Q000737:chemistry / Q000633:toxicity; D020366:Methylmethacrylate / Q000737:chemistry* / Q000633:toxicity; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity; D013365:Submandibular Gland Neoplasms / Q000473:pathology; D013696:Temperature; D014407:Tumor Cells, Cultured
D000179:Acrylates; D008051:Lipid Bilayers; D008081:Liposomes; D008567:Membranes, Artificial; D008689:Methacrylates; D009153:Mutagens; D020366:Methylmethacrylate; D015060:1,2-Dipalmitoylphosphatidylcholine; C032490:n-butyl acrylate; C040833:ethyl acrylate; C016284:butyl methacrylate