The relationship between intracellular lysosomal rupture and cell death caused by silica was studied in P388D, macrophages. After 3 h of exposure to 150 Jig silica in medium containing 1 .8 mM Ca", 60% of the cells were unable to exclude trypan blue . In the absence of extracellular Ca", however, all of the cells remained viable . Phagocytosis of silica particles occurred to the same extent in the presence or absence of Ca" . The percentage of P388D, cells killed by silica depended on the dose and the concentration of Ca" in the medium . Intracellular lysosomal rupture after exposure to silica was measured by acridine orange fluorescence or histochemical assay of horseradish peroxidase . With either assay, 60% of the cells exposed to 150 Ftg silica for 3 h in the presence or absence of Ca" showed intracellular lysosomal rupture, whereas cell death occurred only in the presence of Ca" . Intracellular lysosomal rupture was not associated with measurable degradation of total DNA, RNA, protein, or phospholipid or accelerated turnover of exogenous horseradish peroxidase . Pretreatment with promethazine (20 pg/ml) protected 80% of P388D, macrophages against silica toxicity although lysosomal rupture occurred in 60-70% of the cells. Intracellular lysosomal rupture was prevented in 80% of the cells by pretreatment with indomethacin (5 x 10 -5 M), yet 40-50% of the cells died after 3 h of exposure to 150 p,g silica in 1 .8 mM extracellular Ca" . The calcium ionophore A23187 also caused intracellular lysosomal rupture in 90-98% of the cells treated for 1 h in either the presence or absence of extracellular Ca t+ . With the addition of 1 .8 mM Ca 2+, 80% of the cells was killed after 3 h, whereas all of the cells remained viable in the absence ofCa". These experiments suggest that intracellular lysosomal rupture is not causally related to the cell death caused by silica or A23187 . Cell death is dependent on extracellular Ca 2+ and may be mediated by an influx of these ions across the plasma membrane permeability barrier damaged directly by exposure to these toxins .Lysosomes participate in the physiological turnover of cellular macromolecules (15), limited autophagy of cellular organelles, and storage of undegradable materials (13). At least 60 different enzymes capable of digesting nucleic acids, proteins, lipids, and carbohydrates (6) are contained in these membrane-bound organelles, separated from their potential substrates. Endogenous or exogenous substances enter the lysosome by fusion of autophagic (13) or endocytic vacuoles (34) with lysosomes. This confines hydrolytic processes to the lysosome and presumably prevents unregulated intracellular digestion (13) .In various pathological states, cell injury may be produced by either extracellular or intracellular release of lysosomal enzymes (16). Extracellular release of lysosomal enzymes ac-

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Photoaldrin, photodieldrin, and photoheptachlor are more toxic than their corresponding parent compounds (aldrin, dieldrin, and heptachlor) to freshwater invertebrates and vertebrates, and to adult houseflies. The increase in toxicity is very significant in the case of the amphipod, Gammarus (1.5-12 times), bluegill fry (3.6 5.7 times), mosquito larvae, Aedas (2.3-6 times), minnow fry (2.5 times), and the isopid, Asellus (2 times). The greatest increases occur with photodieldrin which is 12 and 5 times more toxic than dieldrin, respectively, to Gammarus, and to bluegill fry, and with photoatdrin which is 6 and 4 times more toxic than aldrin, respectively, to mosquito larvae and bluegill fry. The toxicities of the photoisomers of isodrin and chlordene are generally less than those of their parent compounds to all the organisms tested. The basis of the differences in toxicities of the chlorinated cyclodiene photoisomers appears to be related to their chemical structure which possibly affects their action at the site(s) of toxic action and/or detoxication. The acidic proton present at the secondary chloride in photoatdrin, photodieldrin, and photoheptachlor possibly is responsible for the formation of charge-transfer complexes between components of the nerve and the mixed-function oxidase; the latter enzyme apparently dehydrochlorinates these photo products to their corresponding, more toxic ketones. The absence of such protons in photoisodrin and photochlordene renders them incapable of forming such ketones. The inhibition of these reactions by sesamex in house flies increases the stability of the chlorinated cyclodiene insecticides and, thus, significantly affects their toxicity. The conversion of photoaldrin, photodieldrin, and photoheptachlor to more-toxic and lipophilic ketones warrants additional studies of their accumulation and subsequent concentration by the food chain.The photolysis of chlorinated cyclodiene insecticide chemicals has been reported by workers in several laboratories (Rosen and Sutherland 1966, Rosen et al. 1969, Henderson and Crosby 1967, Khan et al., Benson et al. 1971. Studies, in the laboratories of the present authors, have shown that photoaldrin (PA), photodieldrin (PD), and photoheptachlor (PH) are several times more toxic to houseflies, aquatic insects, crustacea, other aquatic tPresent address: College

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