1. Introduction

2. Materials and Methods

2.3. Growing environment and experimental metal varinates Cu²⁺ (CuSO₄) and Pb²⁺ (Pb(C₂H₃O₂)₂)

Four concentrations of Cu²⁺ and Pb²⁺ were used in this study to determine the effect on lifecycle proliferation. Due to the varying toxicity limits between Cu²⁺ and Pb²⁺ according to the literature we used intermediate epidermal variants to determine the proliferation inhibition concentration (>IC₅₀) in the four genotypes of D. melanogaster studied (wild, white, brown and white-vestigial) and to compare the toxicity levels between the two metals.

The experimental variants used were:

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normal environment with grey (control) [81];

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medium with grey, supplemented with copper sulphate solution CuSO₄ -5H₂O (0.50 mM, 1.00 mM, 2.00 mM and 4.00 mM);

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medium with grey, supplemented with Pb(C₂H₃O₂)_2.·3H₂O lead acetate solution (0.50 mM, 1.00 mM, 2.00 mM and 4.00 mM);

Determination of the inhibition index (CI₅₀) of proliferation following exposure to Cu²⁺ (CuSO₄) and Pb²⁺ (Pb(C₂H₃O₂)₂)

After pregrafting the experimental variants, Drosophila melanogaster adults were inoculated in a 1:1 ratio (♀ : ♂) for the wild-type and mutant genotypes: white, brown and white-vestigial.

The experiment was carried out in three replicates during the life cycle (egg-adult, Figure 2) ,during which the proliferation of different genotypes of Drosophila melanogaster was monitored under normal conditions and exposed to Cu²⁺ and Pb²⁺ concentrations of 0.50 mM, 1.00 mM, 2.00 mM and 4.00 mM.

In the research, the impact of Cu²⁺ and Pb²⁺ was monitored at all developmental stages of Drosophila melanogaster (egg, larvae I, II, III, pupa and adult) (Figure 1) in order to determine the prolificacy as well as their inhibition concentrations.

After the establishment of the proliferation indices under normal conditions, they were compared with the experimental variants with different concentrations of Cu²⁺ and Pb²⁺ to determine the proliferation inhibition index (IC) according to formula (1):

$$\mathit{I}\mathit{C}=100-\frac{\mathit{N}\mathit{u}\mathit{m}\mathit{b}\mathit{e}\mathit{r} \mathit{o}\mathit{f} \mathit{i}\mathit{n}\mathit{d}\mathit{i}\mathit{v}\mathit{i}\mathit{d}\mathit{u}\mathit{a}\mathit{l}\mathit{s} \mathit{i}\mathit{n} \mathit{e}\mathit{x}\mathit{p}\mathit{e}\mathit{r}\mathit{i}\mathit{m}\mathit{e}\mathit{n}\mathit{t}\mathit{a}\mathit{l} \mathit{g}\mathit{r}\mathit{o}\mathit{u}\mathit{p}}{\mathit{N}\mathit{u}\mathit{m}\mathit{b}\mathit{e}\mathit{r} \mathit{o}\mathit{f} \mathit{i}\mathit{n}\mathit{d}\mathit{i}\mathit{v}\mathit{i}\mathit{d}\mathit{u}\mathit{a}\mathit{l}\mathit{s} \mathit{i}\mathit{n} \mathit{c}\mathit{o}\mathit{n}\mathit{t}\mathit{r}\mathit{o}\mathit{l} \mathit{g}\mathit{r}\mathit{o}\mathit{u}\mathit{p}}\ast 100$$

(1)

The proliferation inhibition index >IC₅₀ was considered the maximum toxicity level of the metal taken in the study [89,90].

Figure 2. Developmental stages of Drosophila melanogaster larvae, (a.1)- larva stage I, (a.2)- larva stage II, (a.3)- larva stage III, (a.4)- larva pupation; Evolution of pupal to adult formation: (b.1)- pupal, (b.2)- hatching, (b.3)- hatched pupal, (b.4)- adult;.

Figure 2. Developmental stages of Drosophila melanogaster larvae, (a.1)- larva stage I, (a.2)- larva stage II, (a.3)- larva stage III, (a.4)- larva pupation; Evolution of pupal to adult formation: (b.1)- pupal, (b.2)- hatching, (b.3)- hatched pupal, (b.4)- adult;.

3. Results

3.1. Influence of genotype, concentration and type of metal Cu²⁺ and Pb²⁺ on proliferation in Drosophila melanogaster

In the study of the influence of different wild-type genotypes (control) and variations between brown, white and white-vestigial mutant genotypes, a significant difference in the number of larvae formed in stages I, II and III under different experimental conditions was observed.

The results show a directly proportional correlation between the concentrations of heavy metals used and their type (Cu²⁺ and Pb²⁺), as well as the nature of the genotype, in terms of the number of larvae formed (p < 0.001).

There was also a significant influence of genotype on the number of individuals resulting from exposure to these metals.

Thus, from the results obtained, it can be deduced that the type of genotype studied can exert a significantly different influence on the number of individuals resulting from exposure to Cu²⁺ and Pb²⁺, thus confirming the significant role of genetic predisposition to toxicity (Table 1).

As in the larval stage, the influence of genotype and metal concentrations used was found to show significant variation in prolificacy levels throughout the life cycle, including in pupation and adult formation (p < 0.001) (Table 2).

Analysis of the interaction between the genetic factor and metal concentration levels (Cu²⁺ and Pb²⁺ ) significantly influenced proliferation in D. melanogaster throughout the life cycle, both in the larval stages (Table 1) and in the pupal and adult formation process (Table 2) (p < 0.001). Thus, as concentration increases, proliferation capacity specifically affects certain genotypes, with some being more tolerant (showing a lower inhibition concentration) and others more sensitive.

Looking at the interaction between concentration and metal type (Cu²⁺ or Pb²⁺), it had a significant impact on the number of individuals during the developmental cycle (p < 0.001). This reflects differences in the response of proliferation rates depending on the type of metal to which D. melanogaster genotypes are exposed.

The results obtained show the same impact of decreased prolificacy for both Cu²⁺, and Pb²⁺, obtaining the same effect of decreased number of inidivids in larval stages of pupal formation (Genotype*Metal, Concentration*Genotype: Metal, p >0.05). Toxicity levels (degree of inhibition of proliferation, >IC₅₀) are influenced by genotype, concentrations and type of metal (Cu²⁺ or Pb²⁺) used in the medium (Concentration, Genotype, Metal, Concentration*Genotype, Concentration*Metal, p <0.001) (Table 1 and Table 2).

Table 2. Analysis of factors involved in the process of inhibition of proliferation at different concentrations of copper (CuSO₄) and lead (Pb(C₂H₃O₂)₂ in pupal and adult formation.

Table 2. Analysis of factors involved in the process of inhibition of proliferation at different concentrations of copper (CuSO₄) and lead (Pb(C₂H₃O₂)₂ in pupal and adult formation.

	Analysis factor	df	SS	S2	F	Pr(>F)
Pupal stage	Concentration	4	24437	6109	203.090	< 2e-16 ***
	Genotype	3	5526	1842	61.234	< 2e-16 ***
	Metal	1	1687	1687	56.094	1.45e-13 ***
	Concentration: Genotype	12	1132	94	3.136	0.000211 ***
	Concentration:Metal	4	585	146	4.861	0.000691 ***
	Genotype:Metal	3	80	27	0.884	0.448785 Ns
	Concentration: Genotype: Metal	12	179	15	0.496	0.918151 Ns
	Residuals	1060	31886	30
Adult stage	Concentration	4	12209	3052.3	135.964	< 2e-16 ***
	Genotype	3	4569	1522.9	67.837	< 2e-16 ***
	Metal	1	893	893.5	39.799	5.55e-10 ***
	Concentration: Genotype	12	551	45.9	2.044	0.0189 *
	Concentration:Metal	4	274	68.5	3.051	0.0166 *
	Genotype:Metal	3	65	21.7	0.968	0.4075 Ns
	Concentration: Genotype: Metal	12	89	7.4	0.331	0.9836 Ns
	Residuals	586	13155	22.4

Note: SS- sum of square, dF-degrees of freedom; S² -mean square. “Ns”-not significant, “*”- p < 0.05, “**”- p < 0.01, ***significant at p < 0.001.

3.2. Influence of copper (CuSO₄) on proliferation in Drosophila melanogaster during the life cycle (egg-adult)

Investigations of the prolificacy rate of Drosophila melanogaster genotypes at various copper concentrations show a decrease directly proportional to the increase in copper concentration, both in the three larval developmental stages (stage I, II and III) and in the pupal and adult formation stages (Table 3).

Significant differences were observed in the response to copper concentrations between the genotypes used (p < 0.05). Brown and white-vestigial genotypes showed higher sensitivity to the highest Cu⁺² concentrations compared to wild and white genotypes.

The wild genotype showed prolificacy rate values below 50% (>IC₅₀ ) at copper concentrations of 4.00 mM in larval stages I, II and III. Close values of proliferation inhibition >IC₅₀ were observed at 2.00 mM concentration of Cu⁺². The same toxicity effect was observed in pupal and adult formation with >IC₅₀ values being present at 4.00 mM concentration (Table 3).

Table 3. Results on the proliferation of D. melanogaster genotypes following exposure to various concentrations of copper.

Table 3. Results on the proliferation of D. melanogaster genotypes following exposure to various concentrations of copper.

Genotype	Concentration (mM)	Copper (CuSO4)
		StageI	IC	StageII	IC	StageIII	IC	Pupal	IC	Adult	IC
		Mean		Mean		Mean		Mean		Mean
wild	Control	35.97a	0.00	28.33a	0.00	26.39a	0.00	25.41a	0.00	24.87a	0.00
	0.50	29.85b	17.03	24.58abc	13.24	22.24ab	15.73	20.67ab	18.66	20.27abc	18.50
	1.00	25.41bcd	29.37	19.58cdef	30.88	17.85bcde	32.38	15.67cde	38.34	16.40cdef	34.05
	2.00	21.56de	40.06	16.58defgh	41.47	15.03defg	43.05	13.33def	47.52	14.20def	42.90
	4.00	13.23fgh	63.22	10.14ijk	64.22	9.24hijk	64.98	7.90ghi	68.92	8.39gh	66.26
brown	Control	27.08bc	0.00	20.83cde	0.00	19.52bcd	0.00	18.74bc	0.00	17.73bcd	0.00
	0.50	22.28cde	17.71	17.83defgh	14.40	16.39cdef	15.99	14.96cdef	20.16	14.47def	18.42
	1.00	19.97de	26.23	16.03efgh	23.07	14.88efg	23.76	13.04def	30.43	12.73defg	28.20
	2.00	16.85efg	37.78	12.56hij	39.73	11.67ghij	40.22	10.22fgh	45.45	10.80fgh	39.10
	4.00	10.82hi	60.04	7.03kl	66.27	6.48kl	66.77	6.00hi	67.98	6.94hi	60.84
white	Control	30.54b	0.00	26.64ab	0.00	26.18a	0.00	24.48a	0.00	22.31ab	0.00
	0.50	28.00bc	8.31	21.47bcd	19.40	19.82bc	24.31	17.26bcd	29.50	18.33bcd	17.83
	1.00	22.33cde	26.87	17.14defgh	35.66	16.30cdef	37.73	14.07cdef	42.51	14.27def	36.06
	2.00	17.85ef	41.56	13.53fghi	49.22	12.30fghi	53.01	10.85efg	55.67	11.67efgh	47.71
	4.00	10.46hi	65.74	8.33ghij	68.72	7.18jkl	72.57	7.30ghi	70.18	6.56hi	70.62
white-vestigial	Control	23.10cd	0.00	21.85bcd	0.00	19.70bc	0.00	18.56bc	0.00	16.93bcde	0.00
	0.50	19.79de	14.32	18.42defg	15.72	15.94cdefg	19.08	14.63cdef	21.16	13.87defg	18.11
	1.00	17.05efg	26.19	15.19fghi	30.47	13.27efgh	32.62	12.74def	31.34	11.33efgh	33.07
	2.00	11.51ghi	50.17	9.03jkl	58.69	8.45ijkl	57.08	7.22ghi	61.08	6.27hi	62.99
	4.00	5.97i	74.14	4.53l	79.27	4.58l	76.77	3.64i	80.37	2.94i	82.63

*Superscript letters are assigned based on the results of the Tukey pairwise comparison test, indicating the significance levels of each column value obtained relative to the copper concentration and exposure time. The highest-ranked values are denoted, beginning with the first letter “a”. Similar superscript letters indicate statistically non-significant differences between the obtained values (p >0.05).**IC denotes the prolificity inhibitaion concentration of copper.

For the brown genotype, at the concentration of 4.00 mM Cu⁺², the results indicate a decrease in proliferation for larval stages I, II and III (>IC₅₀), highlighting a manifestation of increased toxicity in this genotype (p <0.05). A significant decrease in the number of pupae and adults compared to the control variant is also noted, indicating the negative impact of copper on their formation (p <0.05).

In the case of the white genotype, the concentration of 4.00 mM (>IC₅₀) of copper shows the same toxic effect, causing a reduction in the proliferation of this genotype during the life cycle.

The highest sensitivity was recorded in the white-vestigial genotype in which the 2.00 mM Cu⁺² concentration (>IC₅₀) showed a decrease in proliferation of more than 50% compared to the control group for all developmental stages (p <0.05).

According to the results obtained (Table 3 and Figure 3), the proliferation rate of the genotypes was inhibited by the presence of copper in all larval stages, showing the significant reduction of the proliferation rate starting with the dose of 0.50 mM Cu⁺²(p <0.05).

In the early stages of the developmental cycle, concentrations of 0.50-1.00 mM Cu⁺² resulted in decreases in the proliferation rate, which increased as the concentration of Cu⁺² increased.

Pup and adult formation of the genotypes studied was influenced directly proportional to increasing concentrations for all stages followed (Table 3 and Figure 4).

Thus, from the presented results it was evident that the value of >IC₅₀ at the concentration of 4.00 mM is present in all studied genotypes (4/4). At 2.00 mM concentration of Cu⁺² the white-vestigial genotype showed the >IC₅₀ value throughout the development cycle (1/4).

The results obtained in this study highlight the impact of copper concentrations (CuSO₄) on the proliferation of Drosophila melanogaster during their life cycle, showing an inhibition with increasing copper concentration and genotype under study.

3.3. Influence of lead (Pb(C₂H₃O₂)₂ on proliferation in Drosophila melanogaster during the life cycle (egg-adult)

Analysis of the number of stage I, II and III larvae of Drosophila melanogaster genotypes exposed to varying concentrations of Pb²⁺ revealed significant differences in the rate of proliferation as an effect of toxicity. The results showed significant variation in the number of individuals developed under different experimental conditions.

Investigations found that genotype had a significant influence on development in D. melanogaster following exposure, confirming a higher genetic predisposition to toxicity for certain genotypes. The highest values of prolificacy were recorded for the wild and white genotypes, the average values for the brown genotype and the lowest values for the white-western genotype (Table 4). The >IC₅₀ value at all developmental stages is present only in the white-vestigial genotype at a concentration of 4.00 mM (1/4, of genotypes).

In the early stages of the developmental cycle, larval stages exposed to concentrations ranging from 0.50 to 1.00 mM of lead exhibited a decrease in prolificacy. However, this decrease was not statistically significant concerning genotype prolificacy (p >0.05).

The wild genotype showed a significant reduction in the number of larvae in stages I. II and III at higher concentrations, especially at 4.00 mM. The same trend was observed for the white and brown genotypes, suggesting a common sensitivity to lead.

As for the white-vestigial genotype, a more pronounced sensitivity to lead was observed. with a significant reduction in larval numbers in stages I, II and III starting at 1.00 mM concentration. in contrast to the other genotypes which showed a higher tolerance at this concentration. The results suggest that genotypes show different responses to lead concentrations. influencing development in D. melanogaster to varying degrees.

Figure 5. Effect of lead on different genotypes of Drosophila melanogaster in adult formation: (a)- wild genotype. (b)- brown genotype, (c)- white mutant genotype, (d)- white-vestigial mutant genotype.

Figure 5. Effect of lead on different genotypes of Drosophila melanogaster in adult formation: (a)- wild genotype. (b)- brown genotype, (c)- white mutant genotype, (d)- white-vestigial mutant genotype.

Figure 6. Effect of lead on different genotypes of Drosophila melanogaster in adult formation: (a)- wild wild genotype (b)- brown genotype (c)- white mutant genotype (d)- white-vestigial mutant genotype.

Figure 6. Effect of lead on different genotypes of Drosophila melanogaster in adult formation: (a)- wild wild genotype (b)- brown genotype (c)- white mutant genotype (d)- white-vestigial mutant genotype.

Analysing the influence of Drosophila melanogaster genotypes on the number of pupae and adults obtained we found that the diversity of genotypes had a significant impact on the results. while also influencing the number of pupae in the control samples (p <0.001). In the case of lead exposure, the results obtained indicate a significant link between lead concentration and the effects generated.

Studies on mutant genotypes revealed that the white-vestigial genotype showed significantly fewer pupae formed in most of the variants studied, compared to the wild wild genotype which showed the highest tolerance at the pupal and adult stages.

Analysis of the effect of lead in Drosophila melanogaster reveals the significant impact of this metal on the development and health of organisms highlighting the importance of further research in this field and the development of effective strategies for environmental and public health protection.

Comparative study of toxicity effects on drosophila melanogaster at various concentrations of lead and copper

The comparative study of copper and lead toxicity revealed significant variations in the formation of pupae and the emergence of adult flies. The analysis of toxicity differences demonstrated that copper exhibited higher toxicity at both low and high concentrations compared to lead. In the context of adult development, it was observed that at a concentration of 0.50 mM, no significant differences between the two metals were identified (p < 0.05).

Figure 7. Effect of copper on various genotypes of Drosophila melanogaster in adult development.

Figure 7. Effect of copper on various genotypes of Drosophila melanogaster in adult development.

These differences persisted across other concentrations, indicating a continuous dominant effect of copper toxicity over that of lead. Consequently, the level of significance increased with rising concentrations. Therefore, at a concentration of 1.00 mM, the toxicity degree was significantly more pronounced for copper with p < 0.05 compared to lead. At concentrations of 2.00 mM and 4.00 mM, the degree of significance reached p < 0.001. The intervals were significantly different from each other (Figure 8) and also compared to the control group. These findings demonstrate a more acute toxic effect of copper compared to lead. This outcome might be inherently understandable considering that copper (CuSO₄) is often used as an antimicrobial and antibacterial agent, playing a crucial regulatory role in homeostasis, whereas the accumulation of lead exhibits a significantly different toxicological profile.

The study on D. melanogaster can provide valuable insights into both types of toxicity, considering its rapid life cycle and the ease with which multiple generations can be generated and observed.

4. Discussion

5. Conclusions

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