Inhibitory Action of Radiolytic Compounds on Cell
Function
O. L. KLAMERTH
With 3 Figures
Abstract
Glyoxal and malondialdehyde are cytotoxic for cells in culture; the primary
site of attack is DNA. Its rate of synthesis is inhibited more profoundly than that
of protein and RNA. m-RNA synthesis is suppressed almost entirely after a 5-hr
treatment with 100 [Lg/ml dialdehyde. Obviously bifunctional aldehydes inhibit
primarily DNA replication, whereas transcription will be stopped later.
Among the products of radiolysis of aqueous sugar solutions, glyoxal
and malondialdehyde are the most important compounds because of their
reactivity and high toxicity. The organo-toxic effect of glyoxal was demonstrated in rabbits [6, 8, 111 and it was found that very small amounts
cause fatal hypoglycemia as a result of insulin excretion through injury
and damage to the B cells of the pancreas. The toxicity of malondialdehyde on rats was reported by CRAWFORD et al. [4]. That irradiated
sugar solutions in general are cytotoxic for cells in culture was first demonstrated by BERRY et al. [2J, but no detailed insight was given into the
mode of action.
The present stud, was undertaken on tissue cultures to elucidate the
toxic effect of both glyoxal and malondialdehyde on the molecular level.
Cells incubated with glyoxal or malondialdehyde separated from the glass
wall, became transparent, and finally disintegrated. The decrease in viable
cell number in relation to glyoxal or malondialdehyde concentration
respectively after treatment for 5 and 24 hrs is shown in Figs. la and lb.
The inhibition of cell growth and multiplication might be causedapart from by nutritional factors-by the prevention of DNA synthesis,
replication, and/or transcription due to abnormal binding and restricted
strand separation. We assume that, besides the inhibitory action on protein synthesis-malondialdehyde, for example, reacts with protein, as
has been demonstrated in [5]-both dialdehydes can react with DNA.
To determine the rate of synthesis of DNA, RNA and protein, pulselabel experiments were performed with the respective labelled precursors.
12 3. Symp. Quant. Hiol.
Function
O. L. KLAMERTH
With 3 Figures
Abstract
Glyoxal and malondialdehyde are cytotoxic for cells in culture; the primary
site of attack is DNA. Its rate of synthesis is inhibited more profoundly than that
of protein and RNA. m-RNA synthesis is suppressed almost entirely after a 5-hr
treatment with 100 [Lg/ml dialdehyde. Obviously bifunctional aldehydes inhibit
primarily DNA replication, whereas transcription will be stopped later.
Among the products of radiolysis of aqueous sugar solutions, glyoxal
and malondialdehyde are the most important compounds because of their
reactivity and high toxicity. The organo-toxic effect of glyoxal was demonstrated in rabbits [6, 8, 111 and it was found that very small amounts
cause fatal hypoglycemia as a result of insulin excretion through injury
and damage to the B cells of the pancreas. The toxicity of malondialdehyde on rats was reported by CRAWFORD et al. [4]. That irradiated
sugar solutions in general are cytotoxic for cells in culture was first demonstrated by BERRY et al. [2J, but no detailed insight was given into the
mode of action.
The present stud, was undertaken on tissue cultures to elucidate the
toxic effect of both glyoxal and malondialdehyde on the molecular level.
Cells incubated with glyoxal or malondialdehyde separated from the glass
wall, became transparent, and finally disintegrated. The decrease in viable
cell number in relation to glyoxal or malondialdehyde concentration
respectively after treatment for 5 and 24 hrs is shown in Figs. la and lb.
The inhibition of cell growth and multiplication might be causedapart from by nutritional factors-by the prevention of DNA synthesis,
replication, and/or transcription due to abnormal binding and restricted
strand separation. We assume that, besides the inhibitory action on protein synthesis-malondialdehyde, for example, reacts with protein, as
has been demonstrated in [5]-both dialdehydes can react with DNA.
To determine the rate of synthesis of DNA, RNA and protein, pulselabel experiments were performed with the respective labelled precursors.
12 3. Symp. Quant. Hiol.