Investigation of differences in sensitivity between 3 strains of Daphnia magna (crustacean Cladocera) exposed to malathion (organophosphorous pesticide).

Acute and chronic ecotoxic effects of organophosphorous insecticide malathion (Fyfanon 50 EC 500 g L(-1)) were investigated on three strains of Daphnia magna. The nominal effective concentrations immobilizing 50% (EC50) of Daphnia after 24 and 48 h were 0.53 and 0.36 µg L(-1), 0.70 and 0.44 µg L(-1), and 0.75 and 0.46 µg L(-1) for the strains 1, 2, and 3 respectively. There was an increase in malathion ecotoxicity with time of exposure as confirmed by chronic studies. In fact, after 21 days of exposure, significant effects on survival (lowest observed effect concentration or LOECs) were recorded at malathion concentrations of 22, 220 and 230 ng L(-1) for strains 1, 2 and 3 respectively. Other endpoints were also examined, including reproduction (with different parameters), body length and embryo toxicity. ICs10 and ICs20 were calculated for these different parameters. ICs10 ranged from 4.7 to more than 220 ng L(-1) for the three tested strains. The most sensitive parameter was the number of neonates per adult (ICs10 = 4.7 and 10.8 ng L(-1) for strains 1 and 2 respectively) or the number of broods (IC10 = 10 ng L(-1) for strain 3). Moreover, an increase in embryo development abnormalities was observed at the two highest tested malathion concentrations. Abnormalities comprised undeveloped second antennae, curved or unextended shell spines, and curved post-abdomen spines in live neonates. Results suggest that malathion could act as an endocrine disruptor in D. magna as it interferes with development. It also induces a significant decrease in acetylcholinesterase (AChE) activities for the three strains. Both strains 2 and 3 seemed more sensitive (LOECs = 60 ng L(-1)) than strain 1 (LOEC = 120 ng L(-1)). Our results suggest that the AChE activity response can also be used as a biomarker of inter-strain (or inter-clonal) susceptibility (i.e. strain (or clone)-specific response).

Mathematical modeling of bone marrow--peripheral blood dynamics in the disease state based on current emerging paradigms, part I.

Stemming from current emerging paradigms related to the cancer stem cell hypothesis, an existing mathematical model is expanded and used to study cell interaction dynamics in the bone marrow and peripheral blood. The proposed mathematical model is described by a system of nonlinear differential equations with delay, to quantify the dynamics in abnormal hematopoiesis. The steady states of the model are analytically and numerically obtained. Some conditions for the local asymptotic stability of such states are investigated. Model analyses suggest that malignancy may be irreversible once it evolves from a nonmalignant state into a malignant one and no intervention takes place. This leads to the proposition that a great deal of emphasis be placed on cancer prevention. Nevertheless, should malignancy arise, treatment programs for its containment or curtailment may have to include a maximum and extensive level of effort to protect normal cells from eventual destruction. Further model analyses and simulations predict that in the untreated disease state, there is an evolution towards a situation in which malignant cells dominate the entire bone marrow - peripheral blood system. Arguments are then advanced regarding requirements for quantitatively understanding cancer stem cell behavior. Among the suggested requirements are, mathematical frameworks for describing the dynamics of cancer initiation and progression, the response to treatment, the evolution of resistance, and malignancy prevention dynamics within the bone marrow - peripheral blood architecture.