Patterns of porphyrin accumulation in response to chemicals in chick embryo liver cells

Abstract

Four patterns of porphyrin accumulation were observed by high-pressure liquid chromatography when chemicals were added to chick embryo liver cells. These patterns provide a guide to the site of action of the chemicals. Protoporphyrin accumulated in response to 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine (DDC), a result consistent with its ability to inhibit ferrochelatase. Uroporphyrin and heptacarboxylic acid porphyrin accumulated in response to 3,3',4,4'-tetrachlorobiphenyl, 2,2',4,4',6,6'-hexachlorobiphenyl, and 3,5-diethoxycarbonyl-2,4,6-trimethylpyridine, a result suggesting inhibition of uroporphyrinogen decarboxylase. Coproporphyrin was the major porphyrin to accumulate in response to allylisopropylacetamide, aromatic amides, and steroids, a result suggesting inhibition of coproporphyrinogen oxidase. A mixture of uroporphyrin, heptacarboxylic acid porphyrin and coproporphyrin accumulated in response to aromatic di- and mono-esters, aliphatic diesters, and aliphatic amides. The pattern observed after addition of excess delta-aminolevulinic acid (ALA) the endogenous substrate of the pathway to the cells was proto- greater than copro- greater than uro-porphyrin. This pattern resembled that produced by DDC but by none of the other chemicals. It was concluded that porphyrin accumulation can not be attributed solely to the induction of ALA-synthetase. It appears that porphyrin-inducing chemicals exert an additional effect on one or other of the enzymes of the heme biosynthetic pathway.

Suitability of carboxylated porphyrin profiles as a biochemical indicator in whitefish (Coregonus clupeaformis) exposed to bleached kraft pulp mill effluent

“…The accumulation of HCP and coproporphyrin may be caused by a blockage of UROD and CPG activity by components of BKME. The effect is similar to that observed in the previous studies in birds, pike, and chick embryo liver cell culture (Marks et al, 1983;Koss et al, 1986;Kennedy and Fox, 1990).…”

“…The porphyrin profile seems to be more specific than the EROD activity and different toxic substances are expectd to cause different types of porphyrin patterns (Marks, 1985). The porphyrin pattern observed in the present study is not identical to any of types of porphyrin patterns reported in the previous studies on exposure to a variety of chlorinated compounds (Marks et al, 1983;Kennedy and Fox, 1990). Further studies on relationship between the porphyrin patterns and toxic chemicals may be useful to identify the toxic substances in BKME.…”

“…The use of porphyrin profiles as a biochemical indi-cator in mammals and chicken embryo liver cell culture exposed to toxic agents has been evaluated by Marks (1985). Chemicals, such as halogenated aromatic hydrocarbons, pesticides, and metals, can cause a change of porphyrin profiles or increase the total porphyrins in humans, rats, mice, birds, and chick embryo liver cell culture (Elder, 1978;Koss et al, 1983;Marks et al, 1983;Marks, 1985;Carpenter et al, 1985;Rifkind et al, 1985;Sano et al, 1985;Rizzardini et al, 1988;Brady and Lock, 1992). This toxic effect is very specific and different halogenated aromatic compounds lead to different types of porphyrin patterns in chick embryo liver cell culture (Marks et al, 1983).…”

“…Chemicals, such as halogenated aromatic hydrocarbons, pesticides, and metals, can cause a change of porphyrin profiles or increase the total porphyrins in humans, rats, mice, birds, and chick embryo liver cell culture (Elder, 1978;Koss et al, 1983;Marks et al, 1983;Marks, 1985;Carpenter et al, 1985;Rifkind et al, 1985;Sano et al, 1985;Rizzardini et al, 1988;Brady and Lock, 1992). This toxic effect is very specific and different halogenated aromatic compounds lead to different types of porphyrin patterns in chick embryo liver cell culture (Marks et al, 1983). Recent studies have also shown an increase of highly carboxylated porphyrins (HCP, i.e., sum of uro-, hepta-, hexa-, and pentaporphyrin) in wild birds from the Great Lakes (Fox et al, 1988;Kennedy and Fox, 1990).…”

Inhibition of ferrochelatase and accumulation of porphyrins in mouse hepatocyte cultures exposed to porphyrinogenic chemicals

“…In contrast in chick embryo liver cells exposed to ALA, protoporphyrin accounted for most of the porphyrin accumulating (Marks et al 1983), suggesting that in chick hepatocytes ferrochelatase activity is rate limiting. These data suggest that there may be significant differences in the kinetic properties of enzymes of the haem biosynthetic pathway in different species.…”